RESUMO
Asthma is a common chronic respiratory disease affecting more than 300 million people worldwide. Clinical features of asthma and its immunological and molecular etiology vary significantly among patients. An understanding of the complexities of asthma has evolved to the point where precision medicine approaches, including microbiome analysis, are being increasingly recognized as an important part of disease management. Lung and gut microbiota play several important roles in the development, regulation, and maintenance of healthy immune responses. Dysbiosis and subsequent dysregulation of microbiota-related immunological processes affect the onset of the disease, its clinical characteristics, and responses to treatment. Bacteria and viruses are the most extensively studied microorganisms relating to asthma pathogenesis, but other microbes, including fungi and even archaea, can potently influence airway inflammation. This review focuses on recently discovered connections between lung and gut microbiota, including bacteria, fungi, viruses, and archaea, and their influence on asthma.
Assuntos
Asma/imunologia , Asma/microbiologia , Trato Gastrointestinal , Pulmão , Microbiota/imunologia , Animais , Asma/patologia , Asma/fisiopatologia , Disbiose/imunologia , Trato Gastrointestinal/imunologia , Trato Gastrointestinal/microbiologia , Trato Gastrointestinal/parasitologia , Trato Gastrointestinal/virologia , Humanos , Pulmão/imunologia , Pulmão/microbiologia , Pulmão/parasitologia , Pulmão/virologia , Sistema Respiratório/imunologia , Sistema Respiratório/microbiologia , Sistema Respiratório/parasitologia , Sistema Respiratório/virologiaRESUMO
Microbial infections are recognized by the innate immune system both to elicit immediate defense and to generate long-lasting adaptive immunity. To detect and respond to vastly different groups of pathogens, the innate immune system uses several recognition systems that rely on sensing common structural and functional features associated with different classes of microorganisms. These recognition systems determine microbial location, viability, replication and pathogenicity. Detection of these features by recognition pathways of the innate immune system is translated into different classes of effector responses though specialized populations of dendritic cells. Multiple mechanisms for the induction of immune responses are variations on a common design principle wherein the cells that sense infections produce one set of cytokines to induce lymphocytes to produce another set of cytokines, which in turn activate effector responses. Here we discuss these emerging principles of innate control of adaptive immunity.
Assuntos
Imunidade Adaptativa , Células Dendríticas/imunologia , Imunidade Inata , Subpopulações de Linfócitos/imunologia , Animais , Bactérias/imunologia , Citocinas/genética , Citocinas/imunologia , Células Dendríticas/microbiologia , Células Dendríticas/parasitologia , Células Dendríticas/virologia , Fungos/imunologia , Regulação da Expressão Gênica , Helmintos/imunologia , Humanos , Intestinos/imunologia , Intestinos/microbiologia , Intestinos/parasitologia , Intestinos/virologia , Pulmão/imunologia , Pulmão/microbiologia , Pulmão/parasitologia , Pulmão/virologia , Subpopulações de Linfócitos/microbiologia , Subpopulações de Linfócitos/parasitologia , Subpopulações de Linfócitos/virologia , Receptores de Reconhecimento de Padrão/genética , Receptores de Reconhecimento de Padrão/imunologia , Pele/imunologia , Pele/microbiologia , Pele/parasitologia , Pele/virologia , Vírus/imunologiaRESUMO
We examined the role of innate cells in acquired resistance to the natural murine parasitic nematode, Nippostrongylus brasiliensis. Macrophages obtained from lungs as late as 45 d after N. brasiliensis inoculation were able to transfer accelerated parasite clearance to naive recipients. Primed macrophages adhered to larvae in vitro and triggered increased mortality of parasites. Neutrophil depletion in primed mice abrogated the protective effects of transferred macrophages and inhibited their in vitro binding to larvae. Neutrophils in parasite-infected mice showed a distinct transcriptional profile and promoted alternatively activated M2 macrophage polarization through secretory factors including IL-13. Differentially activated neutrophils in the context of a type 2 immune response therefore prime a long-lived effector macrophage phenotype that directly mediates rapid nematode damage and clearance.
Assuntos
Imunidade Adaptativa/imunologia , Macrófagos/imunologia , Neutrófilos/imunologia , Nippostrongylus/imunologia , Infecções por Strongylida/imunologia , Animais , Adesão Celular/imunologia , Adesão Celular/fisiologia , Células Cultivadas , Citocinas/genética , Citocinas/imunologia , Citocinas/metabolismo , Resistência à Doença/imunologia , Feminino , Citometria de Fluxo , Interações Hospedeiro-Parasita/imunologia , Interleucina-13/genética , Interleucina-13/imunologia , Interleucina-13/metabolismo , Subunidade alfa de Receptor de Interleucina-4/genética , Subunidade alfa de Receptor de Interleucina-4/imunologia , Subunidade alfa de Receptor de Interleucina-4/metabolismo , Larva/imunologia , Larva/fisiologia , Pulmão/imunologia , Pulmão/metabolismo , Pulmão/parasitologia , Macrófagos/metabolismo , Camundongos Endogâmicos BALB C , Camundongos Knockout , Neutrófilos/metabolismo , Nippostrongylus/fisiologia , Análise de Sequência com Séries de Oligonucleotídeos , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Infecções por Strongylida/genética , Infecções por Strongylida/parasitologia , Transcriptoma/imunologiaRESUMO
INTRODUCTION: Alveolar echinococcosis (AE), caused by the larval forms of Echinococcus multilocularis, is a zoonotic disease affecting the liver, lungs, lymph nodes, kidneys, brain, bones, thyroid, and other organs. Diagnosing AE in a non-endemic area is usually challenging. With the rapid development and increasing application of sequencing techniques in recent years, metagenomic next-generation sequencing (mNGS) has become a powerful tool for diagnosing rare infectious diseases. CASE PRESENTATION: A 45-year-old woman was admitted to the hospital for the presence of pulmonary shadows for more than 3 months. The lung computed tomography (CT) at a local hospital revealed scattered solid and quasi-circular nodules in the left upper lobe, left lower lobe, right middle lobe, and right lower lobe. The largest nodule was located in the dorsal part of the right lung, measuring 2.0 × 1.7 × 1.5 cm. Moreover, abdominal CT revealed one space-occupying lesion each in the left and right lobes. The pathological analysis of the lung biopsy specimen revealed infiltration of lymphocytes, plasma cells, and eosinophils in the alveolar wall and interstitial area. No pathogenic bacteria were observed in the sputum smear and culture tests. There were no parasite eggs in the stool. The mNGS of the lung puncture tissue revealed 6156 sequence reads matching E. multilocularis; thus, the condition was diagnosed as AE. Albendazole 400 mg was administered twice daily, and the patient was stable during follow-up. CONCLUSION: This case emphasizes the role of mNGS in diagnosing AE. As a novel, sensitive, and accurate diagnostic method, mNGS could be an attractive approach for facilitating early diagnosis and prompt treatment of infectious diseases, especially when the infection was caused by rare pathogens.
Assuntos
Equinococose , Echinococcus multilocularis , Sequenciamento de Nucleotídeos em Larga Escala , Pulmão , Metagenômica , Humanos , Feminino , Pessoa de Meia-Idade , Animais , Pulmão/parasitologia , Pulmão/patologia , Pulmão/diagnóstico por imagem , Metagenômica/métodos , Echinococcus multilocularis/genética , Echinococcus multilocularis/isolamento & purificação , Equinococose/diagnóstico , Equinococose/parasitologia , Tomografia Computadorizada por Raios X , Albendazol/uso terapêutico , Equinococose Pulmonar/diagnóstico , Equinococose Pulmonar/parasitologia , Equinococose Pulmonar/diagnóstico por imagemRESUMO
Allergic asthma, driven by T helper 2 cell-mediated immune responses to common environmental antigens, remains the most common respiratory disease in children. Perfluorinated chemicals (PFCs) are environmental contaminants of great concern, because of their wide application, persistence in the environment, and bioaccumulation. PFCs associate with immunological disorders including asthma and attenuate immune responses to vaccines. The influence of PFCs on the immunological response to allergens during childhood is unknown. We report here that a major PFC, perfluorooctane sulfonate (PFOS), inactivates house dust mite (HDM) to dampen 5-wk-old, early weaned mice from developing HDM-induced allergic asthma. PFOS further attenuates the asthma protective effect of the microbial product lipopolysaccharide (LPS). We demonstrate that PFOS prevents desensitization of lung epithelia by LPS, thus abolishing the latter's protective effect. A close mechanistic study reveals that PFOS specifically binds the major HDM allergen Der p1 with high affinity as well as the lipid A moiety of LPS, leading to the inactivation of both antigens. Moreover, PFOS at physiological human (nanomolar) concentrations inactivates Der p1 from HDM and LPS in vitro, although higher doses did not cause further inactivation because of possible formation of PFOS aggregates. This PFOS-induced neutralization of LPS has been further validated in primary human cell models and extended to an in vivo bacterial infection mouse model. This study demonstrates that early life exposure of mice to a PFC blunts airway antigen bioactivity to modulate pulmonary inflammatory responses, which may adversely affect early pulmonary health.
Assuntos
Ácidos Alcanossulfônicos/farmacologia , Antígenos de Dermatophagoides/imunologia , Asma/imunologia , Asma/parasitologia , Fluorocarbonos/farmacologia , Hipersensibilidade/imunologia , Hipersensibilidade/parasitologia , Ácidos Alcanossulfônicos/química , Animais , Antígenos de Dermatophagoides/química , Asma/complicações , Asma/genética , Células Dendríticas/imunologia , Escherichia coli , Feminino , Fluorocarbonos/química , Perfilação da Expressão Gênica , Hipersensibilidade/complicações , Hipersensibilidade/genética , Imunomodulação/efeitos dos fármacos , Imunomodulação/genética , Lipopolissacarídeos , Pulmão/imunologia , Pulmão/microbiologia , Pulmão/parasitologia , Pulmão/patologia , Camundongos Endogâmicos BALB C , Modelos Moleculares , Pseudomonas aeruginosa/fisiologia , Pyroglyphidae/fisiologiaRESUMO
Pathogen interactions arising during coinfection can exacerbate disease severity, for example when the immune response mounted against one pathogen negatively affects defense of another. It is also possible that host immune responses to a pathogen, shaped by historical evolutionary interactions between host and pathogen, may modify host immune defenses in ways that have repercussions for other pathogens. In this case, negative interactions between two pathogens could emerge even in the absence of concurrent infection. Parasitic worms and tuberculosis (TB) are involved in one of the most geographically extensive of pathogen interactions, and during coinfection worms can exacerbate TB disease outcomes. Here, we show that in a wild mammal natural resistance to worms affects bovine tuberculosis (BTB) severity independently of active worm infection. We found that worm-resistant individuals were more likely to die of BTB than were nonresistant individuals, and their disease progressed more quickly. Anthelmintic treatment moderated, but did not eliminate, the resistance effect, and the effects of resistance and treatment were opposite and additive, with untreated, resistant individuals experiencing the highest mortality. Furthermore, resistance and anthelmintic treatment had nonoverlapping effects on BTB pathology. The effects of resistance manifested in the lungs (the primary site of BTB infection), while the effects of treatment manifested almost entirely in the lymph nodes (the site of disseminated disease), suggesting that resistance and active worm infection affect BTB progression via distinct mechanisms. Our findings reveal that interactions between pathogens can occur as a consequence of processes arising on very different timescales.
Assuntos
Búfalos/imunologia , Resistência à Doença , Hemoncose/microbiologia , Pulmão/imunologia , Linfonodos/imunologia , Tricostrongilose/microbiologia , Tuberculose Bovina/microbiologia , Animais , Antinematódeos/farmacologia , Búfalos/microbiologia , Búfalos/parasitologia , Bovinos , Coinfecção , Progressão da Doença , Eosinófilos/efeitos dos fármacos , Eosinófilos/imunologia , Eosinófilos/microbiologia , Eosinófilos/parasitologia , Fezes/parasitologia , Feminino , Fenbendazol/farmacologia , Hemoncose/tratamento farmacológico , Hemoncose/mortalidade , Hemoncose/parasitologia , Haemonchus/efeitos dos fármacos , Haemonchus/genética , Haemonchus/patogenicidade , Imunoglobulina A/sangue , Pulmão/efeitos dos fármacos , Pulmão/microbiologia , Pulmão/parasitologia , Linfonodos/efeitos dos fármacos , Linfonodos/microbiologia , Linfonodos/parasitologia , Mastócitos/efeitos dos fármacos , Mastócitos/imunologia , Mastócitos/microbiologia , Mastócitos/parasitologia , Mycobacterium bovis/crescimento & desenvolvimento , Mycobacterium bovis/patogenicidade , Índice de Gravidade de Doença , Análise de Sobrevida , Tricostrongilose/tratamento farmacológico , Tricostrongilose/mortalidade , Tricostrongilose/parasitologia , Trichostrongylus/efeitos dos fármacos , Trichostrongylus/genética , Trichostrongylus/patogenicidade , Tuberculose Bovina/tratamento farmacológico , Tuberculose Bovina/mortalidade , Tuberculose Bovina/parasitologiaRESUMO
This study represents the first investigation into the occurrence and identification of Metastrongylus spp. in wild boars (Sus scrofa) in Iran, utilizing both molecular and morphological methods. Thirteen wild boars from Kerman Province were examined, with 92.3% found to be infected with at least one species of Metastrongylus. Mixed infections were observed in 38.46% of the animals. Morphological and molecular analyses confirmed the presence of M. pudendotectus and M. salmi, with prevalence rates of 76.9% and 53.9%, respectively. Histopathological examination revealed transverse and longitudinal sections of Metastrongylus parasites within the airways, causing partial to complete obstruction, interstitial pneumonia, and inflammatory responses. The study also highlights the public health significance of these parasites. The higher prevalence observed compared to earlier studies suggests changes in environmental conditions, host dynamics, or agricultural practices as possible factors, warranting further investigation. The findings underscore the need for comprehensive surveillance and control measures to mitigate the risk of zoonotic transmission, particularly in regions with significant wild and domestic swine populations. This study contributes to the understanding of Metastrongylus spp. distribution and their pathological impact, emphasizing the ecological importance of wild boars and the necessity for continued monitoring and research to prevent and control infections in both animal and human populations.
Assuntos
Metastrongyloidea , Infecções por Strongylida , Sus scrofa , Doenças dos Suínos , Animais , Irã (Geográfico)/epidemiologia , Infecções por Strongylida/veterinária , Infecções por Strongylida/parasitologia , Infecções por Strongylida/epidemiologia , Sus scrofa/parasitologia , Doenças dos Suínos/parasitologia , Doenças dos Suínos/epidemiologia , Suínos , Metastrongyloidea/isolamento & purificação , Metastrongyloidea/classificação , Metastrongyloidea/genética , Prevalência , Pulmão/parasitologia , DNA de Helmintos/genética , Masculino , Análise de Sequência de DNA , Coinfecção/parasitologia , Coinfecção/veterinária , Coinfecção/epidemiologiaRESUMO
Malaria is a hazardous disease caused by Plasmodium parasites and often results in lethal complications, including malaria-associated acute respiratory distress syndrome (MA-ARDS). Parasite sequestration in the microvasculature is often observed, but its role in malaria pathogenesis and complications is still incompletely understood. We used skeleton binding protein-1 (SBP-1) KO parasites to study the role of sequestration in experimental MA-ARDS. The sequestration-deficiency of these SBP-1 KO parasites was confirmed with bioluminescence imaging and by measuring parasite accumulation in the lungs with RT-qPCR. The SBP-1 KO parasites induced similar lung pathology in the early stage of experimental MA-ARDS compared to wildtype (WT) parasites. Strikingly, the lung pathology resolved subsequently in more than 60% of the SBP-1 KO infected mice, resulting in prolonged survival despite the continuous presence of the parasite. This spontaneous disease resolution was associated with decreased inflammatory cytokine expression measured by RT-qPCR and lower expression of cytotoxic markers in pathogenic CD8+ T cells in the lungs of SBP-1 KO infected mice. These data suggest that SBP-1-mediated parasite sequestration and subsequent high parasite load are not essential for the development of experimental MA-ARDS but inhibit the resolution of the disease.
Assuntos
Pulmão/parasitologia , Malária/complicações , Proteínas de Membrana/deficiência , Plasmodium berghei/patogenicidade , Proteínas de Protozoários/metabolismo , Síndrome do Desconforto Respiratório/prevenção & controle , Animais , Progressão da Doença , Feminino , Pulmão/metabolismo , Pulmão/patologia , Malária/parasitologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Proteínas de Protozoários/genética , Síndrome do Desconforto Respiratório/metabolismo , Síndrome do Desconforto Respiratório/parasitologia , Síndrome do Desconforto Respiratório/patologiaRESUMO
Contributions by basophils to allergic and helminth immunity remain incompletely defined. Using sensitive interleukin 4 (Il4) reporter alleles, we demonstrate here that basophil IL-4 production occurs by a CD4(+) T cell-dependent process restricted to the peripheral tissues affected. We genetically marked and achieved specific deletion of basophils and found that basophils did not mediate T helper type 2 (T(H)2) priming in vivo. Two-photon imaging confirmed that basophils did not interact with antigen-specific T cells in lymph nodes but engaged in prolonged serial interactions with T cells in lung tissues. Although targeted deletion of IL-4 and IL-13 in either CD4(+) T cells or basophils had a minimal effect on worm clearance, deletion from both lineages demonstrated a nonredundant role for basophil cytokines in primary helminth immunity.
Assuntos
Basófilos/imunologia , Interleucina-4/imunologia , Pulmão/imunologia , Infecções por Strongylida/imunologia , Animais , Basófilos/metabolismo , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/metabolismo , Feminino , Citometria de Fluxo , Proteínas de Fluorescência Verde/genética , Proteínas de Fluorescência Verde/metabolismo , Helmintíase Animal/imunologia , Helmintíase Animal/metabolismo , Helmintíase Animal/parasitologia , Interações Hospedeiro-Parasita/imunologia , Humanos , Interleucina-13/genética , Interleucina-13/imunologia , Interleucina-13/metabolismo , Interleucina-4/genética , Interleucina-4/metabolismo , Fígado/imunologia , Fígado/metabolismo , Fígado/parasitologia , Pulmão/metabolismo , Pulmão/parasitologia , Pneumopatias Parasitárias/imunologia , Pneumopatias Parasitárias/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Camundongos Transgênicos , Microscopia de Fluorescência por Excitação Multifotônica , Nippostrongylus/imunologia , Nippostrongylus/fisiologia , Schistosoma mansoni/imunologia , Schistosoma mansoni/fisiologia , Infecções por Strongylida/metabolismo , Infecções por Strongylida/parasitologiaRESUMO
Cardio-pulmonary parasites, such as Angiostrongylus vasorum, Crenosoma vulpis, and Eucoleus aerophilus, pose a significant concern on account of pulmonary and cardiac problems they induce in dogs. While the red fox is known to be a key reservoir host for A. vasorum and may also play a role in transmitting C. vulpis and E. aerophilus, there has been no recent research on these parasites in foxes from Sardinia, with the most current studies dating back to 1986. A survey was conducted on red foxes in Sardinia, where a total of 51 foxes were collected, necropsied, and examined for adult worms in their hearts and lungs. The worms were identified using morphometric analysis and molecular methods. The results showed a 54.9% overall prevalence at dissection: 45.1% of the foxes were positive for E. aerophilus, 17.6% for C. vulpis, and 13.7% for A. vasorum. The molecular analyses validated the morphological characterization. In comparison to previous research, which found 13 out of 85 foxes to be positive for A. vasorum with a prevalence rate of 15.3% and 1 for E. aerophilus with a prevalence of 1.2%, this study showed an increased prevalence of E. aerophilus and C. vulpis, and a decrease in the prevalence of A. vasorum. These results indicate that the red foxes in Sardinia represent a reservoir host for cardio-pulmonary nematodes and it should be considered in the differential diagnosis of respiratory distress syndrome in dogs.
Assuntos
Raposas , Coração , Pulmão , Metastrongyloidea , Infecções por Nematoides , Animais , Cães , Raposas/parasitologia , Coração/parasitologia , Itália/epidemiologia , Infecções por Nematoides/epidemiologia , Infecções por Nematoides/parasitologia , Infecções por Nematoides/transmissão , Infecções por Nematoides/veterinária , Pulmão/parasitologia , Prevalência , Reservatórios de Doenças/parasitologia , Reservatórios de Doenças/veterinária , Masculino , FemininoRESUMO
AIM: Echinococcosis with multi-organ/disseminated involvement is rare in childhood. We aimed to evaluate the clinical and laboratory characteristics and prognosis in paediatric patients with echinococcosis having multiorgan/disseminated involvement. METHOD: We evaluated retrospectively children with echinococcosis with involvement of three or more organs. RESULTS: Thirteen patients were included in the study. The median age was 120 (range 71-189) months. Three (23%) were diagnosed incidentally. Abdominal pain was seen in 5 (38.4%) patients, vomiting in 4 (30.7%), headache in 3 (23%), cough in 2 (15.3%), groin pain in 1 (7.6%), 1 (7.6%) had jaundice and 1 (7.6%) had fever. The median duration of complaints was 48 (0-140) days. The most common tripartite organ was 38.4% (5/13) liver, lung and spleen. Isolated abdominal dissemination was detected in two patients. Two patients had multi-organ involvement and multiple cysts with dissemination. Cyst rupture was observed in three of the patients; recurrent urinary tract infection, hydroureteronephrosis, secondary peritonitis with intra-abdominal abscess, and biliary tract fistula were each observed in one patient. Relapse developed in 3 (23%) patients. CONCLUSION: Echinococcosis is a very slow growing and complex parasitic disease that affects many organs and tissues. In our study, eosinophilia, recurrence, and complications were seen at a higher rate in paediatric patients with multiorgan involvement, who required repetitive surgeries and long-term medical treatment. However, there are scanty data on risk factors, optimum treatment and prognosis.
Assuntos
Equinococose/patologia , Abdome , Dor Abdominal , Adolescente , Criança , Equinococose/complicações , Equinococose/diagnóstico , Equinococose/terapia , Humanos , Fígado/parasitologia , Fígado/patologia , Pulmão/parasitologia , Pulmão/patologia , Estudos Retrospectivos , Baço/parasitologia , Baço/patologiaRESUMO
The bacterial, fungal, and helminthic species that comprise the microbiome of the mammalian host have profound effects on health and disease. Pathogenic viruses must contend with the microbiome during infection and likely have evolved to exploit or evade the microbiome. Both direct interactions between the virions and the microbiota and immunomodulation and tissue remodeling caused by the microbiome alter viral pathogenesis in either host- or virus-beneficial ways. Recent insights from in vitro and murine models of viral pathogenesis have highlighted synergistic and antagonistic, direct and indirect interactions between the microbiome and pathogenic viruses. This review will focus on the transkingdom interactions between human gastrointestinal and respiratory viruses and the constituent microbiome of those tissues.
Assuntos
Microbiota/fisiologia , Vírus/patogenicidade , Animais , Fenômenos Fisiológicos Bacterianos , Bacteriófagos/fisiologia , Fungos/fisiologia , Trato Gastrointestinal/imunologia , Trato Gastrointestinal/microbiologia , Trato Gastrointestinal/parasitologia , Trato Gastrointestinal/virologia , Helmintos/fisiologia , Humanos , Pulmão/imunologia , Pulmão/microbiologia , Pulmão/parasitologia , Pulmão/virologia , Vírus/classificaçãoRESUMO
Asthma is a common respiratory disease currently affecting more than 300 million worldwide and is characterized by airway inflammation, hyperreactivity, and remodeling. It is a heterogeneous disease consisting of corticosteroid-sensitive T-helper cell type 2-driven eosinophilic and corticosteroid-resistant, T-helper cell type 17-driven neutrophilic phenotypes. One pathway recently described to regulate asthma pathogenesis is cholesterol trafficking. Scavenger receptors, in particular SR-BI (scavenger receptor class B type I), are known to direct cellular cholesterol uptake and efflux. We recently defined SR-BI functions in pulmonary host defense; however, the function of SR-BI in asthma pathogenesis is unknown. To elucidate the role of SR-BI in allergic asthma, SR-BI-sufficient (SR-BI+/+) and SR-BI-deficient (SR-BI-/-) mice were sensitized (Days 0 and 7) and then challenged (Days 14, 15, and 16) with a house dust mite (HDM) preparation administered through oropharyngeal aspiration. Airway inflammation and cytokine production were quantified on Day 17. When compared with SR-BI+/+ mice, the HDM-challenged SR-BI-/- mice had increased neutrophils and pulmonary IL-17A production in BAL fluid. This augmented IL-17A production in SR-BI-/- mice originated from a non-T-cell source that included neutrophils and alveolar macrophages. Given that SR-BI regulates adrenal steroid hormone production, we tested whether the changes in SR-BI-/- mice were glucocorticoid dependent. Indeed, SR-BI-/- mice were adrenally insufficient during the HDM challenge, and corticosterone replacement decreased pulmonary neutrophilia and IL-17A production in SR-BI-/- mice. Taken together, these data indicate that SR-BI dampens pulmonary neutrophilic inflammation and IL-17A production in allergic asthma at least in part by maintaining adrenal function.
Assuntos
Asma/metabolismo , Asma/patologia , Antígenos CD36/metabolismo , Inflamação/patologia , Interleucina-17/metabolismo , Neutrófilos/patologia , Insuficiência Adrenal/complicações , Insuficiência Adrenal/imunologia , Animais , Asma/imunologia , Asma/parasitologia , Antígenos CD36/deficiência , Hipersensibilidade/complicações , Pulmão/parasitologia , Pulmão/patologia , Masculino , Camundongos Endogâmicos C57BL , Neutrófilos/imunologia , Ovalbumina/imunologia , Pyroglyphidae/fisiologia , Células Th17/imunologiaRESUMO
The majority of experiments investigating the immune response to gastrointestinal helminth infection use a single bolus infection. However, in situ individuals are repeatedly infected with low doses. Therefore, to model natural infection, mice were repeatedly infected (trickle infection) with low doses of Trichuris muris. Trickle infection resulted in the slow acquisition of immunity reflected by a gradual increase in worm burden followed by partial expulsion. Flow cytometry revealed that the CD4+ T cell response shifted from Th1 dominated to Th2 dominated, which coincided with an increase in Type 2 cytokines. The development of resistance following trickle infection was associated with increased worm expulsion effector mechanisms including goblet cell hyperplasia, Muc5ac production and increased epithelial cell turn over. Depletion of CD4+ T cells reversed resistance confirming their importance in protective immunity following trickle infection. In contrast, depletion of group 2 innate lymphoid cells did not alter protective immunity. T. muris trickle infection resulted in a dysbiotic mircrobiota which began to recover alpha diversity following the development of resistance. These data establish trickle infection as a robust and informative model for analysis of immunity to chronic intestinal helminth infection more akin to that observed under natural infection conditions and confirms the importance of CD4+ T cell adaptive immunity in host protection.
Assuntos
Anticorpos Anti-Helmínticos/imunologia , Hipersensibilidade/imunologia , Imunidade Inata/imunologia , Intestinos/imunologia , Pulmão/imunologia , Tricuríase/imunologia , Trichuris/imunologia , Imunidade Adaptativa , Animais , Anticorpos Anti-Helmínticos/sangue , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/parasitologia , Hipersensibilidade/parasitologia , Intestinos/parasitologia , Intestinos/patologia , Pulmão/parasitologia , Pulmão/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Células Th2/imunologia , Células Th2/parasitologia , Tricuríase/sangue , Tricuríase/parasitologiaRESUMO
Vertical transmission of Toxoplasma gondii leads to adverse pregnancy outcomes depending on the time at which the infection occurs and the immunological state of the mother. C57BL/6 and BALB/c mice have been described as susceptible and resistant mouse lineages to congenital T. gondii infection, respectively. This study aimed to elucidate the systemic and local cytokine profile of pregnant mice infected with T. gondii and whether the expression of the transcription factor FOXP3, related to T regulatory cells, is associated with the resistance/susceptibility of these lineages of mice in the context of experimental congenital toxoplasmosis. For this purpose, C57BL/6 and BALB/c females were orally infected with the T. gondii ME-49 strain on the day of vaginal plug detection or day 14 of gestation, examined 7 or 5 days later, respectively, as models of early and late pregnancy. Cytokine levels were measured systemically and in the uterus/placenta. Additionally, the uterus/placenta were evaluated macroscopically for resorption rates and histologically for parasite and FOXP3 immunostaining. The FOXP3 protein expression was also evaluated by western blotting assay. It was found that, during early pregnancy, the infection leads to high IFN-γ, TNF and IL-6 levels systemically, with the TNF levels being higher in C57BL/6 mice. At the maternal-fetal interface, the infection induced high levels of IFN-γ in both mouse lineages; however, higher levels were observed in BALB/c, while high TNF and IL-6 levels were found in C57BL/6, but not in BALB/c mice. In contrast, in late gestation, T. gondii interfered less strongly with the cytokine profile. In early pregnancy, a reduction of FOXP3 expression at the maternal-fetal interface of infected mice was also observed, and the reduction was larger in C57BL/6 compared with BALB/c mice. Additionally, the parasite was seldom found in the uterus/placenta. Thus, the worse pregnancy outcomes observed in C57BL/6 mice were associated with higher TNF systemically, and TNF and IL-6 at the maternal-fetal interface, with lower FOXP3 expression.
Assuntos
Fatores de Transcrição Forkhead/metabolismo , Interleucina-6/sangue , Troca Materno-Fetal , Resultado da Gravidez , Toxoplasmose Congênita/sangue , Fator de Necrose Tumoral alfa/sangue , Animais , Modelos Animais de Doenças , Feminino , Interferon gama/sangue , Pulmão/parasitologia , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Parasitos/fisiologia , Placenta/embriologia , Placenta/metabolismo , Placenta/parasitologia , Gravidez , Toxoplasma/fisiologia , Toxoplasmose Animal/sangue , Útero/embriologia , Útero/patologiaRESUMO
Infections with protozoan and helminthic parasites affect multiple organs in the mammalian host. Imaging pathogens in their natural environment takes a more holistic view on biomedical aspects of parasitic infections. Here, we focus on selected organs of the thoracic and abdominopelvic cavities most commonly affected by parasites. Parasitic infections of these organs are often associated with severe medical complications or have health implications beyond the infected individual. Intravital imaging has provided a more dynamic picture of the host-parasite interplay and contributed not only to our understanding of the various disease pathologies, but has also provided fundamental insight into the biology of the parasites.
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Interações Hospedeiro-Parasita , Microscopia Intravital/métodos , Parasitos , Doenças Parasitárias , Animais , Feminino , Genitália , Coração/parasitologia , Humanos , Fígado , Pulmão/parasitologia , Masculino , Glândulas Mamárias Humanas , Placenta , GravidezRESUMO
The goal of this study was to analyse the effects of a protein-deficient (PD) diet on antibody-dependent cell-mediated cytotoxicity (ADCC) in vitro against newborn larvae (NBL) of Trichinella spiralis in the lungs of infected rats. Two groups of weaning Wistar rats received a PD diet (6.5% casein) and other two received a control diet (C, 20% casein). After ten days, one group of each diet was infected (PDI and CI ) with muscle larvae. Lung tissue extracts (LTE) and lung cell suspension (LCS) were obtained. PDI had lower titres of anti-NBL antibodies in LTE than CI . In ADCC assays using control cells, NBL mortality percentage was lower with LTE from PDI than LTE from CI (P < .01). In assays using control cytotoxic sera, ADCC was exerted by LCS from CI at all days post-infection (p.i.), but only by LCS from 13 days p.i. from PDI . ADCC assays combining LTE and LCS from the same group showed a lower response for PDI than for CI (P < .0001). LCS from PDI contained lower numbers of neutrophils, eosinophils and FcεRI+ cells than CI . PD may diminish ADCC activity against T spiralis NBL in lungs through alterations in specific antibodies and effector cells.
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Pulmão/imunologia , Deficiência de Proteína/complicações , Trichinella spiralis , Triquinelose/complicações , Animais , Anticorpos Anti-Helmínticos/sangue , Antígenos de Helmintos/imunologia , Feminino , Larva , Pulmão/parasitologia , Ratos , Ratos Wistar , Trichinella spiralis/imunologia , DesmameRESUMO
BACKGROUND: Toxoplasma gondii is a protozoan with worldwide distribution and triggers a strong Th1 immune response in infected susceptible hosts. On the contrary, most helminth infections are characterized by Th2 immune response and the use of helminth-derived antigens to regulate immune response in inflammatory disorders has been broadly investigated. OBJECTIVES: The aim of this study was to investigate whether treatment with Strongyloides venezuelensis antigen extract (SvAg) would alter immune response against T gondii. METHODS: C57BL/6 mice were orally infected with T gondii and treated with SvAg, and parasitological, histological and immunological parameters were investigated. RESULTS: It was observed that SvAg treatment improved survival rates of T gondii-infected mice. At day 7 post-infection, the parasite load was lower in the lung and small intestine of infected SvAg-treated mice than untreated infected mice. Remarkably, SvAg-treated mice infected with T gondii presented reduced inflammatory lesions in the small intestine than infected untreated mice and decreased intestinal and systemic levels of IFN-γ, TNF-α and IL-6. In contrast, SvAg treatment increased T gondii-specific IgA serum levels in infected mice. CONCLUSIONS: S venezuelensis antigen extract has anti-parasitic and anti-inflammatory properties during T gondii infection suggesting as a possible alternative to parasite and inflammation control.
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Antígenos de Helmintos/uso terapêutico , Strongyloides/imunologia , Toxoplasmose/tratamento farmacológico , Animais , Citocinas/análise , Citocinas/sangue , Feminino , Imunoglobulina A/análise , Imunoglobulina A/sangue , Intestino Delgado/parasitologia , Intestino Delgado/patologia , Pulmão/parasitologia , Pulmão/patologia , Camundongos , Camundongos Endogâmicos C57BL , Carga Parasitária , Toxoplasmose Animal/tratamento farmacológicoRESUMO
Schistosome parasites are complex trematode blood flukes responsible for the disease schistosomiasis; a global health concern prevalent in many tropical and sub-tropical countries. While established transcriptomic databases are accessed ad hoc to facilitate studies characterising specific genes or gene families, a more comprehensive systematic updating of gene annotation and survey of the literature to aid in annotation and context is rarely addressed. We have reanalysed an online transcriptomic dataset originally published in 2009, where seven life cycle stages of Schistosoma japonicum were examined. Using the online pathway analysis tool Reactome, we have revisited key data from the original study. A key focus of this study was to improve the interpretation of the gene expression profile of the developmental lung-stage schistosomula, since it is one of the principle targets for worm elimination. Highly enriched transcripts, associated with lung schistosomula, were related to a number of important biological pathways including host immune evasion, energy metabolism and parasitic development. Revisiting large transcriptomic databases should be considered in the context of substantial new literature. This approach could aid in the improved understanding of the molecular basis of parasite biology. This may lead to the identification of new targets for diagnosis and therapies for schistosomes, and other helminths.
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Estágios do Ciclo de Vida , Pneumopatias Parasitárias/parasitologia , Pulmão/parasitologia , Schistosoma japonicum/crescimento & desenvolvimento , Esquistossomose Japônica/parasitologia , Transcriptoma/fisiologia , Análise de Variância , Animais , Degranulação Celular/fisiologia , Conjuntos de Dados como Assunto , Proteínas Facilitadoras de Transporte de Glucose/fisiologia , Interações Hospedeiro-Parasita , Pneumopatias Parasitárias/imunologia , Neutrófilos/fisiologia , Fator 1 de Elongação de Peptídeos/fisiologia , Schistosoma japonicum/genética , Schistosoma japonicum/imunologia , Esquistossomose Japônica/imunologiaRESUMO
Globally, ascariasis ranks as the second leading intestinal helminth infection. However, progress in developing better control strategies, such as vaccines, remains slow-paced. This study aims to measure antibody production and parasite load in male BALB/c mice immunized with crude Ascaris suum intestinal tract homogenate. Thirty-two (32) mice were randomized into: (1) unvaccinated, uninfected (UU); (2) unvaccinated, infected (UI); (3) vaccinated, uninfected (VU); and (4) vaccinated, infected (VI) groups. A 100-µL vaccine containing 50 µg of homogenized A. suum intestines and Complete Freund's Adjuvant (1:1) were introduced intraperitoneally. Immunizations were done on days 0, 10, and 20. Oral gavage with 1000 embryonated eggs was done on day 30. Blood was obtained at day 40. To measure serum IgG levels, indirect ELISA was done. Microtiter plates were coated with 100 µg larval homogenate, and HRP-conjugated anti-mouse IgG was used as secondary antibody. Parasite load was measured in lung and liver tissues. Tukey's HSD of signal to cut-off ratios of absorbance readings obtained in indirect ELISA procedure for the 1:200 serum dilution showed statistically significant difference between the UU and VI (p = 0.026) as well as between UI and VI (p = 0.003) groups. No statistically significant difference in parasite load was observed in the lungs (p = 0.074), liver (p = 0.130), and both lungs and liver (p = 0.101). Immunization elicited a significant larva-directed IgG production. However, there is no significant difference in parasite loads in either lung or liver tissues across all treatment groups as the larval counts obtained from the study were very low and may not be indicative of the actual parasite load in mice.