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1.
BMJ ; 367: l5784, 2019 10 23.
Artigo em Inglês | MEDLINE | ID: mdl-31645334

RESUMO

OBJECTIVE: To assess whether severe psychiatric reactions to trauma and other adversities are associated with subsequent risk of life threatening infections. DESIGN: Population and sibling matched cohort study. SETTING: Swedish population. PARTICIPANTS: 144 919 individuals with stress related disorders (post-traumatic stress disorder (PTSD), acute stress reaction, adjustment disorder, and other stress reactions) identified from 1987 to 2013 compared with 184 612 full siblings of individuals with a diagnosed stress related disorder and 1 449 190 matched individuals without such a diagnosis from the general population. MAIN OUTCOME MEASURES: A first inpatient or outpatient visit with a primary diagnosis of severe infections with high mortality rates (ie, sepsis, endocarditis, and meningitis or other central nervous system infections) from the Swedish National Patient Register, and deaths from these infections or infections of any origin from the Cause of Death Register. After controlling for multiple confounders, Cox models were used to estimate hazard ratios of these life threatening infections. RESULTS: The average age at diagnosis of a stress related disorder was 37 years (55 541, 38.3% men). During a mean follow-up of eight years, the incidence of life threatening infections per 1000 person years was 2.9 in individuals with a stress related disorder, 1.7 in siblings without a diagnosis, and 1.3 in matched individuals without a diagnosis. Compared with full siblings without a diagnosis of a stress related disorder, individuals with such a diagnosis were at increased risk of life threatening infections (hazard ratio for any stress related disorder was 1.47 (95% confidence intervals1.37 to 1.58) and for PTSD was 1.92 (1.46 to 2.52)). Corresponding estimates in the population based analysis were similar (1.58 (1.51 to 1.65) for any stress related disorder, P=0.09 for difference between sibling and population based comparison, and 1.95 (1.66 to 2.28) for PTSD, P=0.92 for difference). Stress related disorders were associated with all studied life threatening infections, with the highest relative risk observed for meningitis (sibling based analysis 1.63 (1.23 to 2.16)) and endocarditis (1.57 (1.08 to 2.30)). Younger age at diagnosis of a stress related disorder and the presence of psychiatric comorbidity, especially substance use disorders, were associated with higher hazard ratios, whereas use of selective serotonin reuptake inhibitors in the first year after diagnosis of a stress related disorder was associated with attenuated hazard ratios. CONCLUSION: In the Swedish population, stress related disorders were associated with a subsequent risk of life threatening infections, after controlling for familial background and physical or psychiatric comorbidities.


Assuntos
Infecções Bacterianas/epidemiologia , Suscetibilidade a Doenças/imunologia , Transtornos de Estresse Traumático/complicações , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Infecções Bacterianas/diagnóstico , Infecções Bacterianas/imunologia , Criança , Feminino , Seguimentos , Humanos , Incidência , Masculino , Anamnese , Pessoa de Meia-Idade , Sistema de Registros/estatística & dados numéricos , Fatores de Risco , Índice de Gravidade de Doença , Irmãos , Transtornos de Estresse Traumático/imunologia , Taxa de Sobrevida , Suécia/epidemiologia , Adulto Jovem
2.
Nat Immunol ; 20(9): 1110-1128, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31406380

RESUMO

In recent years, a population of unconventional T cells called 'mucosal-associated invariant T cells' (MAIT cells) has captured the attention of immunologists and clinicians due to their abundance in humans, their involvement in a broad range of infectious and non-infectious diseases and their unusual specificity for microbial riboflavin-derivative antigens presented by the major histocompatibility complex (MHC) class I-like protein MR1. MAIT cells use a limited T cell antigen receptor (TCR) repertoire with public antigen specificities that are conserved across species. They can be activated by TCR-dependent and TCR-independent mechanisms and exhibit rapid, innate-like effector responses. Here we review evidence showing that MAIT cells are a key component of the immune system and discuss their basic biology, development, role in disease and immunotherapeutic potential.


Assuntos
Apresentação do Antígeno/imunologia , Antígenos de Histocompatibilidade Classe I/imunologia , Antígenos de Histocompatibilidade Menor/imunologia , Células T Invariáveis Associadas à Mucosa/imunologia , Receptores de Antígenos de Linfócitos T/imunologia , Animais , Antígenos/imunologia , Suscetibilidade a Doenças/imunologia , Humanos , Ativação Linfocitária/imunologia , Camundongos , Neoplasias/imunologia
3.
Nat Commun ; 10(1): 3042, 2019 07 17.
Artigo em Inglês | MEDLINE | ID: mdl-31316054

RESUMO

Stress resistance and longevity are positively correlated but emerging evidence indicates that they are physiologically distinct. Identifying factors with distinctive roles in these processes is challenging because pro-longevity genes often enhance stress resistance. We demonstrate that TCER-1, the Caenorhabditis elegans homolog of human transcription elongation and splicing factor, TCERG1, has opposite effects on lifespan and stress resistance. We previously showed that tcer-1 promotes longevity in germline-less C. elegans and reproductive fitness in wild-type animals. Surprisingly, tcer-1 mutants exhibit exceptional resistance against multiple stressors, including infection by human opportunistic pathogens, whereas, TCER-1 overexpression confers immuno-susceptibility. TCER-1 inhibits immunity only during fertile stages of life. Elevating its levels ameliorates the fertility loss caused by infection, suggesting that TCER-1 represses immunity to augment fecundity. TCER-1 acts through repression of PMK-1 as well as PMK-1-independent factors critical for innate immunity. Our data establish key roles for TCER-1 in coordinating immunity, longevity and fertility, and reveal mechanisms that distinguish length of life from functional aspects of aging.


Assuntos
Proteínas de Caenorhabditis elegans/metabolismo , Regulação da Expressão Gênica/fisiologia , Imunidade Inata/genética , Longevidade/genética , Fatores de Alongamento de Peptídeos/metabolismo , Estresse Fisiológico/imunologia , Envelhecimento/genética , Envelhecimento/imunologia , Animais , Caenorhabditis elegans/fisiologia , Proteínas de Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/imunologia , Suscetibilidade a Doenças/imunologia , Fertilidade/genética , Proteínas Quinases Ativadas por Mitógeno/genética , Modelos Animais , Mutação , Fatores de Alongamento de Peptídeos/genética , Fatores de Alongamento de Peptídeos/imunologia , Estresse Fisiológico/genética
4.
Immunity ; 50(6): 1365-1379, 2019 06 18.
Artigo em Inglês | MEDLINE | ID: mdl-31216461

RESUMO

The mammalian intestine is colonized by a wealth of microorganisms-including bacteria, viruses, protozoa, and fungi-that are all integrated into a functional trans-kingdom community. Characterization of the composition of the fungal community-the mycobiota-has advanced further than the much-needed mechanistic studies. Recent findings have revealed roles for the gut mycobiota in the regulation of host immunity and in the development and progression of human diseases of inflammatory origin. We review these findings here while placing them in the context of the current understanding of the pathways and cellular networks that induce local and systemic immune responses to fungi in the gastrointestinal tract. We discuss gaps in knowledge and argue for the importance of considering bacteria-fungal interactions as we aim to define the roles of mycobiota in immune homeostasis and immune-associated pathologies.


Assuntos
Suscetibilidade a Doenças , Gastroenterite/etiologia , Microbioma Gastrointestinal/imunologia , Imunidade , Imunidade Adaptativa , Animais , Suscetibilidade a Doenças/imunologia , Gastroenterite/metabolismo , Homeostase , Interações Hospedeiro-Patógeno/imunologia , Humanos , Imunidade Inata
5.
Parasit Vectors ; 12(1): 248, 2019 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-31109364

RESUMO

BACKGROUND: Mice are susceptible to infections with the rodent filarial nematode Litomosoides sigmodontis and develop immune responses that resemble those of human filarial infections. Thus, the L. sigmodontis model is used to study filarial immunomodulation, protective immune responses against filariae and to screen drug candidates for human filarial diseases. While previous studies showed that type 2 immune responses are protective against L. sigmodontis, the present study directly compared the impact of eosinophils, IL-5, and the IL-4R on the outcome of L. sigmodontis infection. METHODS: Susceptible wildtype (WT) BALB/c mice, BALB/c mice lacking eosinophils (dblGATA mice), IL-5-/- mice, IL-4R-/- mice and IL-4R-/-/IL-5-/- mice were infected with L. sigmodontis. Analyses were performed during the peak of microfilaremia in WT animals (71 dpi) as well as after IL-4R-/-/IL-5-/- mice showed a decline in microfilaremia (119 dpi) and included adult worm counts, peripheral blood microfilariae levels, cytokine production from thoracic cavity lavage, the site of adult worm residence, and quantification of major immune cell types within the thoracic cavity and spleen. RESULTS: Our study reveals that thoracic cavity eosinophil numbers correlated negatively with the adult worm burden, whereas correlations of alternatively activated macrophage (AAM) numbers with the adult worm burden (positive correlation) were likely attributed to the accompanied changes in eosinophil numbers. IL-4R-/-/IL-5-/- mice exhibited an enhanced embryogenesis achieving the highest microfilaremia with all animals becoming microfilariae positive and had an increased adult worm burden combined with a prolonged adult worm survival. CONCLUSIONS: These data indicate that mice deficient for IL-4R-/-/IL-5-/- have the highest susceptibility for L. sigmodontis infection, which resulted in an earlier onset of microfilaremia, development of microfilaremia in all animals with highest microfilariae loads, and an extended adult worm survival.


Assuntos
Suscetibilidade a Doenças/imunologia , Eosinófilos/imunologia , Filariose/imunologia , Interleucina-5/genética , Receptores de Superfície Celular/genética , Animais , Modelos Animais de Doenças , Filariose/sangue , Filarioidea/fisiologia , Técnicas de Inativação de Genes , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Knockout , Microfilárias/imunologia , Ácaros/parasitologia , Transdução de Sinais , Baço/imunologia
6.
Fish Shellfish Immunol ; 91: 264-274, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31128294

RESUMO

Brown trout are polymorphic salmonid species, and it is of importance to investigate whether hybridization affects disease resistance. In this study, susceptibility of brown trout (Salmo trutta Abant, Anatolian, Black Sea, and Caspius) strains and their hybrids to Lactococcus garvieae and Yersinia ruckeri as well as their immune-related gene expression profiles were studied. Results indicated that reciprocal hybridization did not affect disease resistance in brown trout strains. Purebred Black Sea strain of brown trout was the most resistant group against Y. ruckeri, followed by other Black Sea strain hybrids. On the other hand, purebred Anatolian strain was the most resistant group to L. garvieae, followed by other Anatolian strain hybrids. Expression pattern of target genes differed in families, but the overall gene expression was comparatively high in Y. ruckeri infected families. Upregulations were mainly significant at 7 and 28 d post infection while marginal regulations were observed 8 h after infection. Disease resistance status of strains was supported by high expression of immune-related genes such as major histocompatibility complex class I (MHC-I), immunoglobulin light chain (IgL), and antioxidant- and hemoglobin-related gene expression. Therefore, our findings suggest that Black Sea and Anatolian strains could be used to develop fish stock that are resistant for yersiniosis and lactocaccosis, respectively.


Assuntos
Suscetibilidade a Doenças/veterinária , Doenças dos Peixes/imunologia , Infecções por Bactérias Gram-Positivas/veterinária , Truta/genética , Truta/imunologia , Yersiniose/veterinária , Animais , Suscetibilidade a Doenças/imunologia , Infecções por Bactérias Gram-Positivas/imunologia , Hibridização Genética , Lactococcus/fisiologia , Reação em Cadeia da Polimerase em Tempo Real/veterinária , Transcriptoma , Yersiniose/imunologia , Yersinia ruckeri/fisiologia
7.
Nat Commun ; 10(1): 2288, 2019 05 23.
Artigo em Inglês | MEDLINE | ID: mdl-31123265

RESUMO

Recurrent acute respiratory tract infections (ARTIs) affect a large population, yet the specific decisive factors are largely unknown. Here we study a population of 4407 children diagnosed with ARTI, comparing respiratory virome and serum cytokine profiles associated with multiple ARTIs and single ARTI during a six-year period. The relative abundance of Propionibacterium phages is significantly elevated in multiple ARTIs compared to single ARTI group. Serum levels of TIMP-1 and PDGF-BB are markedly increased in multiple ARTIs compared to single-ARTI and non-ARTI controls, making these two cytokines potential predictors for multiple ARTIs. The presence of Propionibacterium phages is associated with higher levels of TIMP-1 and PDGF-BB. Receiver operating characteristic (ROC) curve analyses show that the combination of TIMP-1, PDGF-BB and Propionibacterium phages could be a strong predictor for multiple ARTIs. These findings indicate that respiratory microbe homeostasis and specific cytokines are associated with the onset of multiple ARTIs over time.


Assuntos
Bacteriófagos/isolamento & purificação , Citocinas/sangue , Sistema Respiratório/virologia , Infecções Respiratórias/sangue , Doença Aguda , Bacteriófagos/genética , Criança , Pré-Escolar , Citocinas/imunologia , Suscetibilidade a Doenças/sangue , Suscetibilidade a Doenças/imunologia , Suscetibilidade a Doenças/microbiologia , Feminino , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Humanos , Lactente , Estudos Longitudinais , Masculino , Metagenômica/métodos , Microbiota/genética , Propionibacterium/virologia , Proteômica/métodos , Recidiva , Sistema Respiratório/imunologia , Infecções Respiratórias/imunologia , Infecções Respiratórias/microbiologia , Estudos Retrospectivos
8.
Ticks Tick Borne Dis ; 10(4): 729-741, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30879988

RESUMO

The human Tick-borne encephalitis virus (TBEV) infection is a complex event encompassing factors derived from the virus itself, the vectors, the final host, and the environment as well. Classically, genetic traits stand out among the human factors that modify the susceptibility and progression of infectious diseases. However, and although this is a changing scenario, studies evaluating the genetic factors that affect the susceptibility specifically to TBEV infection and TBEV-related diseases are still scarce. There are already some interesting pieces of evidence showing that some genes and polymorphisms have a real impact on TBEV infection. Also, the inflammatory processes involving tick-human interactions began to be understood in greater detail. This review focuses on the immunogenetic and inflammatory aspects concerning tick-host interactions, TBEV infections, and tick-borne encephalitis. Of note, it has been described that polymorphisms in CD209, GSTM1, IL-10, IL-28B, MMP9, OAS2, OAS3, and TLR3 have a statistically significant impact on TBEV infection. Besides, CCR5, its ligands, and the CCR5Δ32 genetic variant seem to have a very important influence on the infection and its immune responses. Taking this information into consideration, a special discussion regarding the effects of CCR5 on TBEV infection and tick-borne encephalitis will be presented. Emerging topics (such as exosomes, evasins, and CCR5 blockers) involving immunological and inflammatory aspects of TBEV-human interactions will also be addressed. Lastly, the current picture of TBEV infection and the importance to address the TBEV-associated problems through the One Health perspective will be discussed.


Assuntos
Vírus da Encefalite Transmitidos por Carrapatos/genética , Encefalite Transmitida por Carrapatos/imunologia , Interações Hospedeiro-Parasita/genética , Interações Hospedeiro-Parasita/imunologia , Polimorfismo Genético , Receptores CCR5/genética , Animais , Moléculas de Adesão Celular/genética , Progressão da Doença , Suscetibilidade a Doenças/imunologia , Encefalite Transmitida por Carrapatos/genética , Humanos , Imunogenética , Interleucina-10/genética , Lectinas Tipo C/genética , Camundongos , Saúde Única , Receptores CCR5/imunologia , Receptores de Superfície Celular/genética
9.
Int J Mol Sci ; 20(3)2019 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-30736471

RESUMO

As the outermost layer of the body, the skin harbors innumerable and varied microorganisms. These microorganisms interact with the host, and these interactions contribute to host immunity. One of the most abundant genera of skin commensals is Staphylococcus. Bacteria belonging to this genus are some of the most influential commensals that reside on the skin. For example, colonization by Staphylococcus aureus, a well-known pathogen, increases inflammatory responses within the skin. Conversely, colonization by Staphylococcus epidermis, a coagulase-negative staphylococcal species that are prevalent throughout the skin, can be innocuous or beneficial. Thus, manipulating the abundance of these two bacterial species likely alters the skin microbiome and modulates the cutaneous immune response, with potential implications for various inflammation-associated skin diseases. Importantly, before researchers can begin manipulating the skin microbiome to prevent and treat disease, they must first fully understand how these two species can modulate the cutaneous immune response. In this review, we discuss the nature of the interactions between these two bacterial species and immune cells within the skin, discussing their immunogenicity within the context of skin disorders.


Assuntos
Interações Hospedeiro-Patógeno/imunologia , Pele/imunologia , Pele/microbiologia , Infecções Estafilocócicas/imunologia , Infecções Estafilocócicas/microbiologia , Staphylococcus/imunologia , Animais , Portador Sadio , Suscetibilidade a Doenças/imunologia , Humanos , Imunidade , Microbiota , Irmãos , Pele/metabolismo , Infecções Estafilocócicas/metabolismo
10.
Fish Shellfish Immunol ; 86: 497-506, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30513381

RESUMO

Commensal microorganisms present at mucosal surfaces play a vital role in protecting the host organism from bacterial infection. There are multiple factors that contribute to selecting for the microbiome, including host genetics. Flavobacterium psychrophilum, the causative agent of Bacterial Cold Water Disease in salmonids, accounts for acute losses in wild and farmed rainbow trout (Oncorhynchus mykiss). The U.S. National Center for Cool and Cold Water Aquaculture has used family-based selective breeding to generate a line of rainbow trout with enhanced resistance to F. psychrophilum. The goal of this study is to determine whether selective breeding impacts the gut and gill microbiome of the F. psychrophilum-resistant as compared to a background matched susceptible trout line. Mid-gut and gill samples were collected from juvenile fish maintained at high or low stocking densities and microbial diversity assessed by 16S rDNA amplicon sequencing. Results indicate that alpha diversity was significantly higher in the mid-gut of the susceptible line compared to the resistant line, while no significant differences in alpha diversity were observed in the gills. Mycoplasma sp. was the dominant taxon in the mid-gut of both groups, although it was present at a decreased abundance in the susceptible line. We also observed an increased abundance of the potential opportunistic pathogen Brevinema andersonii in the susceptible line. Within the gills, both lines exhibited similar microbial profiles, with Candidatus Branchiomonas being the dominant taxon. Together, these results suggest that selectively bred F. psychrophilum-resistant trout may harness a more resilient gut microbiome, attributing to the disease resistant phenotype. Importantly, interactions between host genetics and environmental factors such as stocking density have a significant impact in shaping trout microbial communities.


Assuntos
Resistência à Doença , Suscetibilidade a Doenças/imunologia , Doenças dos Peixes/imunologia , Infecções por Flavobacteriaceae/veterinária , Brânquias/microbiologia , Microbiota , Oncorhynchus mykiss , Animais , Cruzamento , Suscetibilidade a Doenças/microbiologia , Doenças dos Peixes/microbiologia , Infecções por Flavobacteriaceae/imunologia , Flavobacterium/fisiologia , Microbioma Gastrointestinal
11.
Dev Comp Immunol ; 93: 1-10, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30550777

RESUMO

Neonatal mammals have increased disease susceptibility and sub-optimal vaccine responses. This raises problems in both humans and farm animals. The high prevalence of paratuberculosis in goats and the lack of an effective vaccine against it have a strong impact on the dairy sector, and calls for vaccines optimized for the neonatal immune system. We characterized the composition of the T-cell pool in neonatal kids and adult goats and quantified their turnover rates using in vivo deuterium labelling. From birth to adulthood, CD4+ T-cells were the predominant subset in the thymus and lymph nodes, while spleen and bone marrow contained mainly CD8+ lymphocytes. In blood, CD4+ T-cells were the predominant subset during the neonatal period, while CD8+ T-cells predominated in adults. We observed that thymic mass and cellularity increased during the first 5 months after birth, but decreased later in life. Deuterium labelling revealed that T-cell turnover rates in neonatal kids are considerably higher than in adult animals.


Assuntos
Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Cabras/imunologia , Paratuberculose/epidemiologia , Paratuberculose/imunologia , Fatores Etários , Animais , Animais Recém-Nascidos , Células da Medula Óssea/imunologia , Linfócitos T CD4-Positivos/citologia , Linfócitos T CD8-Positivos/citologia , Deutério/química , Suscetibilidade a Doenças/imunologia , Feminino , Marcação por Isótopo , Linfonodos/citologia , Baço/citologia , Timo/citologia , Vacinas contra a Tuberculose/imunologia
12.
Poult Sci ; 98(4): 1634-1642, 2019 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-30534980

RESUMO

Coccidiosis and necrotic enteritis (NE) are among the most significant diseases affecting the poultry industry. These diseases have become more prominent in the wake of policies to reduce the use of antibiotics in animal production. This has led to more research focused on better understanding the immune system and its responses to pathogen challenge, and thus developing informed strategies to exploit immune responses that can support enhanced disease resistance and growth performance. Some chicken breeds and lines show greater resistance or susceptibility to various diseases, and thus these birds maybe able to shed light on immune processes or pathways that contribute to the more resistant/susceptible state. This review attempts to identify potentially important genes that show some consistency in (relative) up or downregulation in key tissues between the resistant and susceptible chickens. For coccidiosis and NE, relative downregulation of IL-10 and (slightly less consistently) upregulation of IFN-γ appear to be features of more resistant birds. Data for IFN-α, IL-12, and IL-17D are currently less consistent. Gene expression data from NE studies have identified some potentially interesting, perhaps less well understood, immune-related genes (e.g., TCF12, BCL2, IRF2, TRAF3, TAB3, etc.,) that maybe associated with the resistant and/or susceptible phenotype. Salmonella and Campylobacter are important foodborne pathogens harbored by the chicken intestinal tract, while infectious bursal disease and infectious bronchitis are also important viral diseases of poultry. We, therefore, consider whether there are consistent features from resistant/susceptible disease models with these pathogens that relate to findings from the coccidiosis and NE studies. It is not anticipated that ideal immune responses to these pathogens will be identical but rather that consistent elements maybe identified that could help inform breeding or alternative strategies to support general disease resistance and enhanced (and efficient) flock productivity.


Assuntos
Galinhas , Resistência à Doença , Suscetibilidade a Doenças/veterinária , Regulação da Expressão Gênica/imunologia , Doenças das Aves Domésticas/genética , Doenças das Aves Domésticas/imunologia , Imunidade Adaptativa , Animais , Proteínas Aviárias/genética , Proteínas Aviárias/metabolismo , Modelos Animais de Doenças , Suscetibilidade a Doenças/imunologia , Imunidade Inata
13.
Andrologia ; 50(11): e13220, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30569645

RESUMO

Exosomes are endosomal-derived membrane-confined nanovesicles secreted by many (if not all) cell types and isolated from every human bodily fluid examined up to now including plasma, semen, vaginal secretions and breast milk. Exosomes are thought to represent a new player in cell-to-cell communication pathways and immune regulation, and be involved in many physiological and pathological processes. Susceptibility to HIV-1 infection can be impacted by exosomes, while HIV-1 pathogenesis can alter exosomal function and composition. Exosomes isolated from semen and vaginal fluid of healthy individuals can inhibit HIV-1 infection and/or potently block viral transfer in vitro. However, the role of exosomes in HIV-1 transmission and progression is not fully understood yet and some studies show conflicting results, mainly for exosomes isolated from plasma and breast milk. Determining the composition of exosomes from infected donors and studying their interaction with HIV-1 in vitro compared to exosomes isolated from uninfected donors will provide insights into the role exosomes play in HIV-1 transmission during sexual intercourse and breastfeeding.


Assuntos
Exossomos/virologia , Infecções por HIV/transmissão , HIV-1/patogenicidade , Sêmen/citologia , Aleitamento Materno , Coito , Suscetibilidade a Doenças/imunologia , Suscetibilidade a Doenças/virologia , Feminino , Infecções por HIV/imunologia , Infecções por HIV/virologia , HIV-1/imunologia , Interações Hospedeiro-Patógeno/imunologia , Humanos , Masculino , Leite Humano/citologia , Leite Humano/virologia , Sêmen/virologia
14.
PLoS Pathog ; 14(12): e1007457, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30543708

RESUMO

Urinary tract infections (UTI) are extremely common and can be highly recurrent, with 1-2% of women suffering from six or more recurrent episodes per year. The high incidence of recurrent UTI, including recurrent infections caused by the same bacterial strain that caused the first infection, suggests that at least some women do not mount a protective adaptive immune response to UTI. Here we observed in a mouse model of cystitis (bladder infection) that infection with two different clinical uropathogenic Escherichia coli (UPEC) isolates, UTI89 or CFT073, resulted in different kinetics of bacterial clearance and different susceptibility to same-strain recurrent infection. UTI89 and CFT073 both caused infections that persisted for at least two weeks in similar proportions of mice, but whereas UTI89 infections could persist indefinitely, CFT073 infections began to clear two weeks after inoculation and were uniformly cleared within eight weeks. Mice with a history of CFT073 cystitis lasting four weeks were protected against recurrent CFT073 infection after antibiotic therapy, but were not protected against challenge with UTI89. In contrast, mice with a history of UTI89 cystitis lasting four weeks were highly susceptible to challenge infection with either strain after antibiotic treatment. We found that depletion of CD4+ and CD8+ T cell subsets impaired the ability of the host to clear CFT073 infections and rendered mice with a history of CFT073 cystitis lasting four weeks susceptible to recurrent CFT073 cystitis upon challenge. Our findings demonstrate the complex interplay between the broad genetic diversity of UPEC and the host innate and adaptive immune responses during UTI. A better understanding of these host-pathogen interactions is urgently needed for effective drug and vaccine development in the era of increasing antibiotic resistance.


Assuntos
Cistite/imunologia , Suscetibilidade a Doenças/imunologia , Infecções por Escherichia coli/imunologia , Interações Hospedeiro-Patógeno/imunologia , Escherichia coli Uropatogênica/imunologia , Animais , Camundongos , Escherichia coli Uropatogênica/genética
15.
Vet Parasitol ; 264: 64-68, 2018 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-30503094

RESUMO

The establishment rate of Cooperia oncophora related to host age and previous infection was investigated in young calves. Calves of similar age were kept on a feed pad and allocated into multiple groups, based on their age and weight. Two groups (each n = 16) received trickle infections with an ivermectin-susceptible C. oncophora isolate of 2000 or 10,000 infective stage larvae per week while another group (n = 16) was kept as an uninfected control. At intervals over a period of 11 months, two animals from each group were challenged with 15,000 infective stage larvae of an ivermectin-resistant isolate, 25 days later orally treated with ivermectin and 5 days after that slaughtered for worm counts. On three occasions additional calves (n = 2), subjected to the high trickle infection rate, received an ivermectin treatment to remove the existing worm burden, prior to challenge as above. Further calves (n = 4) of similar age were introduced at the beginning and the end of the experiment to determine the effect of larval age on establishment rate. The establishment in the two trickle infection groups declined to <10% within the first three months, which was significantly different from the control group. In the animals receiving the high trickle infection, but an anthelmintic treatment before challenge the establishment rate was not significantly different from the controls. Over the duration of the experiment establishment in the control group declined from 53% to <20%, which was similar to the decrease recorded at the beginning and the end of the experiment in the animals to determine the effect of larval age. The findings indicate that an existing C. oncophora burden had a strong effect on the establishment of incoming larvae in the trickle infected groups, but this was not observed if the existing burden was removed before the final challenge. The decline in establishment rate in the control group was attributed to the age of the larvae and not the age of the calves per se.


Assuntos
Doenças dos Bovinos/parasitologia , Tricostrongiloidíase/imunologia , Tricostrongiloidíase/parasitologia , Animais , Bovinos , Doenças dos Bovinos/tratamento farmacológico , Suscetibilidade a Doenças/imunologia , Suscetibilidade a Doenças/parasitologia , Ivermectina/uso terapêutico , Contagem de Ovos de Parasitas , Trichostrongyloidea/imunologia , Tricostrongiloidíase/tratamento farmacológico
16.
Front Immunol ; 9: 2536, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30473694

RESUMO

The fungal skin disease, chytridiomycosis (caused by Batrachochytrium dendrobatidis and B. salamandrivorans), has caused amphibian declines and extinctions globally since its emergence. Characterizing the host immune response to chytridiomycosis has been a focus of study with the aim of disease mitigation. However, many aspects of the innate and adaptive arms of this response are still poorly understood, likely due to the wide range of species' responses to infection. In this paper we provide an overview of expected immunological responses (with inference based on amphibian and mammalian immunology), together with a synthesis of current knowledge about these responses for the amphibian-chytridiomycosis system. We structure our review around four key immune stages: (1) the naïve immunocompetent state, (2) immune defenses that are always present (constitutive defenses), (3) mechanisms for recognition of a pathogen threat and innate immune defenses, and (4) adaptive immune responses. We also evaluate the current hot topics of immunosuppression and immunopathology in chytridiomycosis, and discuss their respective roles in pathogenesis. Our synthesis reveals that susceptibility to chytridiomycosis is likely to be multifactorial. Susceptible amphibians appear to have ineffective constitutive and innate defenses, and a late-stage response characterized by immunopathology and Bd-induced suppression of lymphocyte responses. Overall, we identify substantial gaps in current knowledge, particularly concerning the entire innate immune response (mechanisms of initial pathogen detection and possible immunoevasion by Bd, degree of activation and efficacy of the innate immune response, the unexpected absence of innate leukocyte infiltration, and the cause and role of late-stage immunopathology in pathogenesis). There are also gaps concerning most of the adaptive immune system (the relative importance of B and T cell responses for pathogen clearance, the capacity and extent of immunological memory, and specific mechanisms of pathogen-induced immunosuppression). Improving our capacity for amphibian immunological research will require selection of an appropriate Bd-susceptible model species, the development of taxon-specific affinity reagents and cell lines for functional assays, and the application of a suite of conventional and emerging immunological methods. Despite current knowledge gaps, immunological research remains a promising avenue for amphibian conservation management.


Assuntos
Anfíbios/imunologia , Quitridiomicetos/imunologia , Dermatomicoses/imunologia , Imunidade Inata/imunologia , Pele/imunologia , Animais , Dermatomicoses/microbiologia , Suscetibilidade a Doenças/imunologia , Memória Imunológica/imunologia , Pele/microbiologia
17.
Front Immunol ; 9: 2589, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30473701

RESUMO

Influenza virus infections particularly when followed by bacterial superinfections (BSI) result in significant morbidities and mortalities especially during influenza pandemics. Type I interferons (IFNs) regulate both anti-influenza immunity and host susceptibility to subsequent BSIs. These type I IFNs consisting of, among others, 14 IFN-α's and a single IFN-ß, are recognized by and signal through the heterodimeric type I IFN receptor (IFNAR) comprised of IFNAR1 and IFNAR2. However, the individual receptor subunits can bind IFN-ß or IFN-α's independently of each other and induce distinct signaling. The role of type I IFN signaling in regulating host susceptibility to both viral infections and BSI has been only examined with respect to IFNAR1 deficiency. Here, we demonstrate that despite some redundancies, IFNAR1 and IFNAR2 have distinct roles in regulating both anti-influenza A virus (IAV) immunity and in shaping host susceptibility to subsequent BSI caused by S. aureus. We found IFNAR2 to be critical for anti-viral immunity. In contrast to Ifnar1 -/- mice, IAV-infected Ifnar2 -/- mice displayed both increased and accelerated morbidity and mortality compared to WT mice. Furthermore, unlike IFNAR1, IFNAR2 was sufficient to generate protection from lethal IAV infection when stimulated with IFN-ß. With regards to BSI, unlike what we found previously in Ifnar1 -/- mice, Ifnar2 -/- mice were not susceptible to BSI induced on day 3 post-IAV, even though absence of IFNAR2 resulted in increased viral burden and an increased inflammatory environment. The Ifnar2 -/- mice similar to what we previously found in Ifnar1 -/- mice were less susceptible than WT mice to BSI induced on day 7 post-IAV, indicating that signaling through a complete receptor increases BSI susceptibility late during clinical IAV infection. Thus, our results support a role for IFNAR2 in induction of anti-IAV immune responses that are involved in altering host susceptibility to BSI and are essential for decreasing the morbidity and mortality associated with IAV infection. These results begin to elucidate some of the mechanisms involved in how the individual IFNAR subunits shape the anti-viral immune response. Moreover, our results highlight the importance of examining the contributions of entire receptors, as individual subunits can induce distinct outcomes as shown here.


Assuntos
Infecções por Orthomyxoviridae/imunologia , Receptor de Interferon alfa e beta/imunologia , Infecções Estafilocócicas/imunologia , Superinfecção/imunologia , Animais , Suscetibilidade a Doenças/imunologia , Feminino , Vírus da Influenza A/imunologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Infecções por Orthomyxoviridae/microbiologia , Staphylococcus aureus/imunologia , Superinfecção/microbiologia , Vacinação/métodos
18.
PLoS One ; 13(11): e0207998, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30475891

RESUMO

Allergic diseases represent a major issue in clinical and experimental immunology due to their high and increasing incidence worldwide. Allergy status of the mother remains the best predictor of an individual's increased risk of allergy development. Dysregulation of the balance between different branches of immune response, chiefly excessive polarization towards Th2, is the underlying cause of allergic diseases. Regulatory T cells (Tregs) play a pivotal role in the timely establishment of physiological immune polarization and are crucial for control of allergy. In our study we used flow cytometry to assess Tregs in cord blood of newborns of healthy (n = 121) and allergic (n = 108) mothers. We observed a higher percentage of Tregs (CD4+CD25+CD127lowFoxP3+) in cord blood of children of allergic mothers. However, the percentage of cells expressing extracellular (PD-1, CTLA-4, GITR) and intracellular (IL-10, TGF-ß) markers of function was lower (significantly for PD-1 and IL-10) within Tregs of these children. Furthermore, Helios- induced Tregs in the cord blood of children of allergic mothers were decreased. These results were supported by a decrease in plasma levels of IL-10 and TGF-ß in cord blood of newborns of allergic mothers, implying lower tolerogenic capacity on the systemic level. Taken together, these findings reflect deficient function of Tregs in the group with higher risk of allergy development. This may be caused by a lower maturation status of the immune system, specifically Tregs, at birth. Such immaturity may represent an important mechanism involved in the increased risk of allergy in children of allergic mothers.


Assuntos
Sangue Fetal/imunologia , Hipersensibilidade/sangue , Hipersensibilidade/imunologia , Linfócitos T Reguladores/imunologia , Citocinas/sangue , Suscetibilidade a Doenças/sangue , Suscetibilidade a Doenças/imunologia , Feminino , Humanos , Imunoglobulina E/sangue , Recém-Nascido , Mães , Risco
19.
Sci Rep ; 8(1): 16501, 2018 11 07.
Artigo em Inglês | MEDLINE | ID: mdl-30405152

RESUMO

Mice lacking Sirt2 spontaneously develop tumors in multiple organs, as well as when expressed in combination with oncogenic KrasG12D, leading to pancreatic tumors. Here, we report that after caerulein-induced pancreatitis, Sirt2-deficient mice exhibited an increased inflammatory phenotype and delayed pancreatic tissue recovery. Seven days post injury, the pancreas of Sirt2-/- mice display active inflammation, whereas wild-type mice had mostly recovered. In addition, the pancreas from the Sirt2-/- mice exhibited extensive tissue fibrosis, which was still present at six weeks after exposure. The mice lacking Sirt2 also demonstrated an enhanced whole body pro-inflammatory phenotype that was most obvious with increasing age. Importantly, an accumulation of a cell population with spontaneous cancerous KrasG12D mutations was observed in the Sirt2-/- mice that is enhanced in the recovering pancreas after exposure to caerulein. Finally, transcriptome analysis of the pancreas of the Sirt2-/- mice exhibited a pro-inflammatory genomic signature. These results suggest that loss of Sirt2, as well as increased age, enhanced the immune response to pancreatic injury and induced an inflammatory phenotype permissive for the accumulation of cells carrying oncogenic Kras mutations.


Assuntos
Ceruletídeo/efeitos adversos , Mutação , Pancreatite/etiologia , Pancreatite/metabolismo , Proteínas Proto-Oncogênicas p21(ras)/genética , Sirtuína 2/genética , Animais , Modelos Animais de Doenças , Suscetibilidade a Doenças/imunologia , Feminino , Predisposição Genética para Doença , Imuno-Histoquímica , Masculino , Camundongos , Camundongos Knockout , Pancreatite/patologia , Regeneração
20.
PLoS One ; 13(11): e0206603, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30427891

RESUMO

A tuberculosis (TB) model that accounts for heterogeneity in host susceptibility to tuberculosis is proposed, with the aim of investigating the implications this may have for the effectiveness of public health interventions. The model examines the possibility that recovered individuals treated from active TB and individuals treated with preventive therapy acquire different levels of immunity. This contrasts with recent studies that assume the two cohorts acquire the same level of immunity, and therefore both groups are reinfected at the same rate. The analysis presented here examines the impact of this assumption when designing intervention strategies. Comparison of reinfection rates between cohorts treated with preventive therapy and recovered individuals who were previously treated for active TB provides important epidemiological insights. It is found that the reinfection rate of the cohort treated with preventive therapy is the one that plays the key role in qualitative changes in TB dynamics. By contrast, the reinfection rate of recovered individuals (previously treated from active TB) plays a minor role. Moreover, the study shows that preventive treatment of individuals during early latency is always beneficial regardless of the level of susceptibility to reinfection. Further, if patients have greater immunity following treatment for late latent infection, then treatment is again beneficial. However, if susceptibility increases following treatment for late latent infection, the effect of treatment depends on the epidemiological setting. That is: (i) in (very) low burden settings, the effect on reactivation predominates and the burden declines with treatment; (ii) in moderate to high burden settings the effect of reinfection predominates and burden increases with treatment. The effect is most dominant between the two reinfection thresholds, RT2 and RT1, respectively associated with individuals being treated with preventive therapy and individuals with untreated late latent TB infection.


Assuntos
Suscetibilidade a Doenças , Modelos Biológicos , Tuberculose/epidemiologia , Tuberculose/terapia , Suscetibilidade a Doenças/epidemiologia , Suscetibilidade a Doenças/imunologia , Humanos , Saúde Pública , Tuberculose/imunologia , Tuberculose/prevenção & controle
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