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2.
Elife ; 102021 09 21.
Artigo em Inglês | MEDLINE | ID: mdl-34544548

RESUMO

Researchers worldwide are repeatedly warning us against future zoonotic diseases resulting from humankind's insurgence into natural ecosystems. The same zoonotic pathogens that cause severe infections in a human host frequently fail to produce any disease outcome in their natural hosts. What precise features of the immune system enable natural reservoirs to carry these pathogens so efficiently? To understand these effects, we highlight the importance of tracing the evolutionary basis of pathogen tolerance in reservoir hosts, while drawing implications from their diverse physiological and life-history traits, and ecological contexts of host-pathogen interactions. Long-term co-evolution might allow reservoir hosts to modulate immunity and evolve tolerance to zoonotic pathogens, increasing their circulation and infectious period. Such processes can also create a genetically diverse pathogen pool by allowing more mutations and genetic exchanges between circulating strains, thereby harboring rare alive-on-arrival variants with extended infectivity to new hosts (i.e., spillover). Finally, we end by underscoring the indispensability of a large multidisciplinary empirical framework to explore the proposed link between evolved tolerance, pathogen prevalence, and spillover in the wild.


Assuntos
Evolução Biológica , Doenças Transmissíveis Emergentes/transmissão , Reservatórios de Doenças , Zoonoses/transmissão , Animais , Doenças Transmissíveis Emergentes/epidemiologia , Doenças Transmissíveis Emergentes/imunologia , Interações Hospedeiro-Patógeno , Humanos , Virulência , Zoonoses/epidemiologia , Zoonoses/imunologia
3.
Cell Rep ; 36(8): 109614, 2021 08 24.
Artigo em Inglês | MEDLINE | ID: mdl-34433041

RESUMO

Zoonotic pathogens, such as COVID-19, reside in animal hosts before jumping species to infect humans. The Carnivora, like mink, carry many zoonoses, yet how diversity in host immune genes across species affect pathogen carriage is poorly understood. Here, we describe a progressive evolutionary downregulation of pathogen-sensing inflammasome pathways in Carnivora. This includes the loss of nucleotide-oligomerization domain leucine-rich repeat receptors (NLRs), acquisition of a unique caspase-1/-4 effector fusion protein that processes gasdermin D pore formation without inducing rapid lytic cell death, and the formation of a caspase-8 containing inflammasome that inefficiently processes interleukin-1ß. Inflammasomes regulate gut immunity, but the carnivorous diet has antimicrobial properties that could compensate for the loss of these immune pathways. We speculate that the consequences of systemic inflammasome downregulation, however, can impair host sensing of specific pathogens such that they can reside undetected in the Carnivora.


Assuntos
Carnívoros/metabolismo , Evolução Molecular , Inflamassomos/metabolismo , Zoonoses/patologia , Animais , Caspase 1/genética , Caspase 1/metabolismo , Caspase 8/metabolismo , Caspases Iniciadoras/genética , Caspases Iniciadoras/metabolismo , Morte Celular , Linhagem Celular , Humanos , Interleucina-1beta/metabolismo , Lipopolissacarídeos/farmacologia , Macrófagos/citologia , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Proteínas NLR/genética , Proteínas NLR/metabolismo , Proteínas Recombinantes de Fusão/biossíntese , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Salmonella typhi/patogenicidade , Zoonoses/imunologia , Zoonoses/parasitologia
4.
Cells ; 10(6)2021 05 23.
Artigo em Inglês | MEDLINE | ID: mdl-34070971

RESUMO

The recent SARS-CoV-2 pandemic has refocused attention to the betacoronaviruses, only eight years after the emergence of another zoonotic betacoronavirus, the Middle East respiratory syndrome coronavirus (MERS-CoV). While the wild source of SARS-CoV-2 may be disputed, for MERS-CoV, dromedaries are considered as source of zoonotic human infections. Testing 100 immune-response genes in 121 dromedaries from United Arab Emirates (UAE) for potential association with present MERS-CoV infection, we identified candidate genes with important functions in the adaptive, MHC-class I (HLA-A-24-like) and II (HLA-DPB1-like), and innate immune response (PTPN4, MAGOHB), and in cilia coating the respiratory tract (DNAH7). Some of these genes previously have been associated with viral replication in SARS-CoV-1/-2 in humans, others have an important role in the movement of bronchial cilia. These results suggest similar host genetic pathways associated with these betacoronaviruses, although further work is required to better understand the MERS-CoV disease dynamics in both dromedaries and humans.


Assuntos
Imunidade Adaptativa/genética , Camelus/virologia , Doenças Transmissíveis Emergentes/imunologia , Infecções por Coronavirus/imunologia , Imunidade Inata/genética , Zoonoses/imunologia , Animais , Anticorpos Antivirais , Brônquios/citologia , Brônquios/fisiologia , COVID-19/genética , COVID-19/imunologia , COVID-19/virologia , Camelus/genética , Camelus/imunologia , Cílios/fisiologia , Doenças Transmissíveis Emergentes/genética , Doenças Transmissíveis Emergentes/transmissão , Doenças Transmissíveis Emergentes/virologia , Infecções por Coronavirus/genética , Infecções por Coronavirus/transmissão , Infecções por Coronavirus/virologia , Reservatórios de Doenças/virologia , Feminino , Predisposição Genética para Doença , Interações entre Hospedeiro e Microrganismos/genética , Interações entre Hospedeiro e Microrganismos/imunologia , Humanos , Masculino , Coronavírus da Síndrome Respiratória do Oriente Médio/imunologia , Coronavírus da Síndrome Respiratória do Oriente Médio/isolamento & purificação , Coronavírus da Síndrome Respiratória do Oriente Médio/patogenicidade , Mucosa Respiratória/citologia , Mucosa Respiratória/fisiologia , SARS-CoV-2/imunologia , SARS-CoV-2/patogenicidade , Emirados Árabes Unidos , Replicação Viral/genética , Replicação Viral/imunologia , Zoonoses/genética , Zoonoses/transmissão , Zoonoses/virologia
5.
mBio ; 12(2)2021 04 13.
Artigo em Inglês | MEDLINE | ID: mdl-33849979

RESUMO

Animals that are competent reservoirs of zoonotic pathogens commonly suffer little morbidity from the infections. To investigate mechanisms of this tolerance of infection, we used single-dose lipopolysaccharide (LPS) as an experimental model of inflammation and compared the responses of two rodents: Peromyscus leucopus, the white-footed deermouse and reservoir for the agents of Lyme disease and other zoonoses, and the house mouse Mus musculus Four hours after injection with LPS or saline, blood, spleen, and liver samples were collected and subjected to transcriptome sequencing (RNA-seq), metabolomics, and specific reverse transcriptase quantitative PCR (RT-qPCR). Differential expression analysis was at the gene, pathway, and network levels. LPS-treated deermice showed signs of sickness similar to those of exposed mice and had similar increases in corticosterone levels and expression of interleukin 6 (IL-6), tumor necrosis factor, IL-1ß, and C-reactive protein. By network analysis, the M. musculus response to LPS was characterized as cytokine associated, while the P. leucopus response was dominated by neutrophil activity terms. In addition, dichotomies in the expression levels of arginase 1 and nitric oxide synthase 2 and of IL-10 and IL-12 were consistent with type M1 macrophage responses in mice and type M2 responses in deermice. Analysis of metabolites in plasma and RNA in organs revealed species differences in tryptophan metabolism. Two genes in particular signified the different phenotypes of deermice and mice: the Slpi and Ibsp genes. Key RNA-seq findings for P. leucopus were replicated in older animals, in a systemic bacterial infection, and with cultivated fibroblasts. The findings indicate that P. leucopus possesses several adaptive traits to moderate inflammation in its balancing of infection resistance and tolerance.IMPORTANCE Animals that are natural carriers of pathogens that cause human diseases commonly manifest little or no sickness as a consequence of infection. Examples include the deermouse, Peromyscus leucopus, which is a reservoir for Lyme disease and several other disease agents in North America, and some types of bats, which are carriers of viruses with pathogenicity for humans. Mechanisms of this phenomenon of infection tolerance and entailed trade-off costs are poorly understood. Using a single injection of lipopolysaccharide (LPS) endotoxin as a proxy for infection, we found that deermice differed from the mouse (Mus musculus) in responses to LPS in several diverse pathways, including innate immunity, oxidative stress, and metabolism. Features distinguishing the deermice cumulatively would moderate downstream ill effects of LPS. Insights gained from the P. leucopus model in the laboratory have implications for studying infection tolerance in other important reservoir species, including bats and other types of wildlife.


Assuntos
Reservatórios de Doenças/microbiologia , Endotoxinas/administração & dosagem , Inflamação/genética , Peromyscus/microbiologia , Zoonoses/imunologia , Zoonoses/microbiologia , Animais , Suscetibilidade a Doenças/etiologia , Suscetibilidade a Doenças/imunologia , Endotoxinas/imunologia , Feminino , Perfilação da Expressão Gênica , Inflamação/imunologia , Doença de Lyme/microbiologia , Masculino , Metabolômica , Camundongos , Camundongos Endogâmicos BALB C , Peromyscus/imunologia , Análise de Sequência de RNA
6.
OMICS ; 25(4): 234-241, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33794117

RESUMO

A key lesson emerging from COVID-19 is that pandemic proofing planetary health against future ecological crises calls for systems science and preventive medicine innovations. With greater proximity of the human and animal natural habitats in the 21st century, it is also noteworthy that zoonotic infections such as COVID-19 that jump from animals to humans are increasingly plausible in the coming decades. In this context, glycomics technologies and the third alphabet of life, the sugar code, offer veritable prospects to move omics systems science from discovery to diverse applications of relevance to global public health and preventive medicine. In this expert review, we discuss the science of glycomics, its importance in vaccine development, and the recent progress toward discoveries on the sugar code that can help prevent future infectious outbreaks that are looming on the horizon in the 21st century. Glycomics offers veritable prospects to boost planetary health, not to mention the global scientific capacity for vaccine innovation against novel and existing infectious agents.


Assuntos
Vacinas contra COVID-19/administração & dosagem , COVID-19/epidemiologia , Glicômica/organização & administração , Pandemias/prevenção & controle , SARS-CoV-2/patogenicidade , Zoonoses/epidemiologia , Animais , COVID-19/imunologia , COVID-19/prevenção & controle , COVID-19/transmissão , Vacinas contra COVID-19/biossíntese , Ecossistema , Saúde Global/economia , Saúde Global/tendências , Humanos , Cooperação Internacional , Vacinação em Massa/métodos , Medicina Preventiva/métodos , SARS-CoV-2/efeitos dos fármacos , Glicoproteína da Espícula de Coronavírus/química , Glicoproteína da Espícula de Coronavírus/imunologia , Vacinas Sintéticas/administração & dosagem , Vacinas Sintéticas/biossíntese , Zoonoses/imunologia , Zoonoses/prevenção & controle , Zoonoses/transmissão
7.
PLoS Negl Trop Dis ; 15(1): e0008633, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33406074

RESUMO

Zoonotic diseases pose a significant health challenge at the human-wildlife interface, especially in Sub-Saharan Africa where ecosystem services contribute significantly to local livelihoods and individual well-being. In Uganda, the fragmented forests of Hoima district, form part of a "biodiversity and emerging infectious disease hotspot" composed of communities with high dependency on these wildlife protected areas, unaware of the associated health risks. We conducted a cross-sectional mixed methods study from March to May 2017 and interviewed 370 respondents, using a semi-structured questionnaire from eight villages neighbouring forest fragments in Hoima District, Uganda. Additionally, a total of ten (10) focus group discussions (FGDs) consisting of 6-10 men or women were conducted to further explore the drivers of hunting and perception of zoonotic disease risks at community level. Qualitative and quantitative data were analysed using content analysis and STATA version 12 respectively. We found twenty-nine percent (29.0%, CI: 24.4-33.9) of respondents were engaged in hunting of wildlife such as chimpanzee (Pan troglodytes) and 45.8% (CI: 40.6-51.0), cane rats (Thryonomyidae spp). Acquisition of animal protein was among the main reasons why communities hunt (55.3%, CI: 50.1-60.4), followed by "cultural" and "medicinal" uses of wildlife and or its parts (22.7%, CI: 18.6-27.4). Results further revealed that hunting and bushmeat consumption is persistent for other perceived reasons like; bushmeat strengthens the body, helps mothers recover faster after delivery, boosts one's immunity and hunting is exercise for the body. However, respondents reported falling sick after consumption of bushmeat at least once (7.9%, CI: 5.3-11.1), with 5.3% (CI: 2.60-9.60) reporting similar symptoms among some family members. Generally, few respondents (37.0%, CI: 32.1-42.2) were aware of diseases transmissible from wildlife to humans, although 88.7% (CI: 85.0-92.0) had heard of Ebola or Marburg without context. Hunting non-human primate poses a health risk compared to edible rats (cane rats) and wild ruminants (cOR = 0.4, 95% CI = 0.1-0.9) and (cOR = 0.7, 95% CI = 0.2-2.1) respectively. Study suggests some of the pathways for zoonotic disease spillover to humans exist at interface areas driven by livelihoods, nutrition and cultural needs. This study offers opportunities for a comprehensive risk communication and health education strategy for communities living at the interface of wildlife and human interactions.


Assuntos
Animais Selvagens , Biodiversidade , Educação em Saúde , Zoonoses/transmissão , Adulto , Animais , Animais Selvagens/virologia , Mordeduras e Picadas , Estudos Transversais , Ecossistema , Feminino , Florestas , Doença pelo Vírus Ebola , Humanos , Masculino , Primatas , Ratos , Inquéritos e Questionários , Uganda , Zoonoses/imunologia
8.
Lancet Infect Dis ; 21(3): 385-395, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33035474

RESUMO

BACKGROUND: Middle East respiratory syndrome (MERS) remains of global public health concern. Dromedary camels are the source of zoonotic infection. Over 70% of MERS coronavirus (MERS-CoV)-infected dromedaries are found in Africa but no zoonotic disease has been reported in Africa. We aimed to understand whether individuals with exposure to dromedaries in Africa had been infected by MERS-CoV. METHODS: Workers slaughtering dromedaries in an abattoir in Kano, Nigeria, were compared with abattoir workers without direct dromedary contact, non-abattoir workers from Kano, and controls from Guangzhou, China. Exposure to dromedaries was ascertained using a questionnaire. Serum and peripheral blood mononuclear cells (PBMCs) were tested for MERS-CoV specific neutralising antibody and T-cell responses. FINDINGS: None of the participants from Nigeria or Guangdong were MERS-CoV seropositive. 18 (30%) of 61 abattoir workers with exposure to dromedaries, but none of 20 abattoir workers without exposure (p=0·0042), ten non-abattoir workers or 24 controls from Guangzhou (p=0·0002) had evidence of MERS-CoV-specific CD4+ or CD8+ T cells in PBMC. T-cell responses to other endemic human coronaviruses (229E, OC43, HKU-1, and NL-63) were observed in all groups with no association with dromedary exposure. Drinking both unpasteurised camel milk and camel urine was significantly and negatively associated with T-cell positivity (odds ratio 0·07, 95% CI 0·01-0·54). INTERPRETATION: Zoonotic infection of dromedary-exposed individuals is taking place in Nigeria and suggests that the extent of MERS-CoV infections in Africa is underestimated. MERS-CoV could therefore adapt to human transmission in Africa rather than the Arabian Peninsula, where attention is currently focused. FUNDING: The National Science and Technology Major Project, National Institutes of Health.


Assuntos
Camelus/imunologia , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/veterinária , Coronavírus da Síndrome Respiratória do Oriente Médio/imunologia , Exposição Ocupacional/estatística & dados numéricos , Linfócitos T/imunologia , Zoonoses/epidemiologia , Zoonoses/imunologia , Adolescente , Adulto , Idoso , Animais , Anticorpos Neutralizantes , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Camelus/virologia , Estudos de Coortes , Infecções por Coronavirus/transmissão , Feminino , Humanos , Leucócitos Mononucleares/imunologia , Masculino , Pessoa de Meia-Idade , Nigéria/epidemiologia , Adulto Jovem , Zoonoses/transmissão , Zoonoses/virologia
9.
Trends Parasitol ; 37(2): 117-129, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33214097

RESUMO

Because most emerging human pathogens originate in mammals, many studies aim to identify host traits that determine the risk of sourcing zoonotic outbreaks. Studies regularly assert that 'fast-lived' mammal species exhibiting greater fecundity and shorter lifespans tend to host more zoonoses; however, the causes of this association remain poorly understood and they cover a range of immune and nonimmune mechanisms. We discuss these drivers in the context of evolutionary ecology and wildlife-human interactions. Ultimately, differentiating these mechanisms will require linking interspecific variation in life history with immunity, pathogen diversity, transmissibility, and zoonotic risk, and critical data gaps currently limit our ability to do so. We highlight sampling and analytical frameworks to address this gap and to better inform zoonotic reservoir prediction.


Assuntos
Interações Hospedeiro-Parasita/imunologia , Longevidade/fisiologia , Doenças Parasitárias/transmissão , Zoonoses/imunologia , Zoonoses/parasitologia , Animais , Biodiversidade , Evolução Biológica , Reservatórios de Doenças/parasitologia , Interação Humano-Animal , Humanos , Risco , Fatores de Tempo , Zoonoses/transmissão
10.
Parasitology ; 148(1): 110-114, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33143775

RESUMO

Visceral leishmaniasis is an endemic protozoonosis observed in over 60 countries, with over 500 000 new cases recorded annually. Although the diagnostic procedure of its symptomatic forms is well established, for asymptomatic patients, who represent about 85% of those infected, there is no consensus on the best method for its identification. Recent studies have presented molecular techniques as viable identification methods, with good sensitivity and specificity indices in asymptomatic individuals. Therefore, we aimed to use molecular methods to assess their effectiveness in identifying the presence of asymptomatic infection by Leishmania infantum (L. infantum) individuals from endemic regions of Brazil. Screening was performed by real-time polymerase chain reaction (qPCR) and confirmed by sequencing the cytochrome B gene. Of the 127 samples [from 608 blood donors who had participated in a previous study, of which 34 were positive by the enzyme-linked immunosorbent assay (ELISA) rK39] tested by qPCR, 31 (24.4%) were positive. In the sequencing of 10 qPCR-positive samples, five were identified as L. infantum. Complimentary samples of the ELISA rK39 and conventional PCR showed only reasonable and low agreement with qPCR, respectively. The qPCR confirmed the presence of infection in five of the 10 sequenced samples, ELISA confirmed three, and the conventional PCR confirmed none.


Assuntos
Doadores de Sangue , Leishmania infantum , Leishmaniose Visceral , Animais , Anticorpos Antiprotozoários/sangue , Infecções Assintomáticas , Brasil , Citocromos b/genética , DNA de Protozoário/genética , Ensaio de Imunoadsorção Enzimática , Humanos , Leishmania infantum/genética , Leishmania infantum/imunologia , Leishmania infantum/isolamento & purificação , Leishmaniose Visceral/diagnóstico , Leishmaniose Visceral/imunologia , Reação em Cadeia da Polimerase em Tempo Real , Sensibilidade e Especificidade , Zoonoses/diagnóstico , Zoonoses/imunologia
11.
Pathog Dis ; 79(1)2021 01 09.
Artigo em Inglês | MEDLINE | ID: mdl-33289808

RESUMO

A vast proportion of coronavirus disease 2019 (COVID-19) individuals remain asymptomatic and can shed severe acute respiratory syndrome (SARS-CoV) type 2 virus to transmit the infection, which also explains the exponential increase in the number of COVID-19 cases globally. Furthermore, the rate of recovery from clinical COVID-19 in certain pockets of the globe is surprisingly high. Based on published reports and available literature, here, we speculated a few immunovirological mechanisms as to why a vast majority of individuals remain asymptomatic similar to exotic animal (bats and pangolins) reservoirs that remain refractile to disease development despite carrying a huge load of diverse insidious viral species, and whether such evolutionary advantage would unveil therapeutic strategies against COVID-19 infection in humans. Understanding the unique mechanisms that exotic animal species employ to achieve viral control, as well as inflammatory regulation, appears to hold key clues to the development of therapeutic versatility against COVID-19.


Assuntos
COVID-19/imunologia , Síndrome da Liberação de Citocina/imunologia , Proteína 3 que Contém Domínio de Pirina da Família NLR/imunologia , Receptores KIR/imunologia , Receptores Semelhantes a Lectina de Células NK/imunologia , Zoonoses/imunologia , Animais , Animais Exóticos/virologia , Doenças Assintomáticas , COVID-19/genética , COVID-19/transmissão , COVID-19/virologia , Quirópteros/virologia , Síndrome da Liberação de Citocina/genética , Síndrome da Liberação de Citocina/prevenção & controle , Síndrome da Liberação de Citocina/virologia , Reservatórios de Doenças , Eutérios/virologia , Expressão Gênica , Especificidade de Hospedeiro , Humanos , Tolerância Imunológica , Imunidade Inata , Interferon beta/deficiência , Interferon beta/genética , Interferon beta/imunologia , Células Matadoras Naturais/imunologia , Células Matadoras Naturais/virologia , Monócitos/imunologia , Monócitos/virologia , Proteína 3 que Contém Domínio de Pirina da Família NLR/deficiência , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Receptores KIR/deficiência , Receptores KIR/genética , Receptores Semelhantes a Lectina de Células NK/deficiência , Receptores Semelhantes a Lectina de Células NK/genética , SARS-CoV-2/patogenicidade , Fator de Necrose Tumoral alfa/deficiência , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/imunologia , Zoonoses/genética , Zoonoses/transmissão , Zoonoses/virologia
12.
Virus Res ; 292: 198235, 2021 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-33232783

RESUMO

The first incidence of COVID-19 was reported in the Wuhan city of Hubei province in China in late December 2019. Because of failure in timely closing of borders of the affected region, COVID-19 spread across like a wildfire through air travel initiating a pandemic. It is a serious lower respiratory track viral infection caused by highly contagious, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Coronavirus including COVID-19 causing SARS-CoV-2 causes zoonotic diseases and thought to be originated from bats. Since its first incidence, the virus has spread all across the world, causing serious human casualties, economic losses, and disrupting global supply chains. As with SARS-CoV, COVID-19 causing SARS-CoV-2 follows a similar path of airborne infection, but is less lethal and more infectious than SARS and MERS. This review focusses on the pathogenesis of SARS-CoV-2, especially on the dysfunctional immune responses following a cytokine storm in severely affected persons. The mode of entry of SARS-CoV-2 is via the angiotensin converting enzyme 2 (ACE-2) receptors present on the epithelial lining of lungs, gastrointestinal tract, and mucus membranes. Older persons with weaker immune system and associated co-morbidities are more vulnerable to have dysfunctional immune responses, as most of them concomitantly have severe hypovitaminosis D. Consequently, causing severe damage to key organs of the body including lungs and the cardiovascular system. Since, vast majority of persons enters to the intensive care units and died, had severe vitamin D deficiency, thus, this area must be investigated seriously. In addition, this article assesses the role of vitamin D in reducing the risk of COVID-19. Vitamin D is a key regulator of the renin-angiotensin system that is exploited by SARS-CoV-2 for entry into the host cells. Further, vitamin D modulates multiple mechanisms of the immune system to contain the virus that includes dampening the entry and replication of SARS-CoV-2, reduces concentration of pro-inflammatory cytokines and increases levels of anti-inflammatory cytokines, enhances the production of natural antimicrobial peptide and activates defensive cells such as macrophages that could destroy SARS-CoV-2. Thus, this article provides the urgency of needed evidences through large population based randomized controlled trials and ecological studies to evaluate the potential role of vitamin D in COVID-19.


Assuntos
COVID-19/imunologia , COVID-19/fisiopatologia , Vitamina D/imunologia , Imunidade Adaptativa , Animais , Ensaios Clínicos como Assunto , Síndrome da Liberação de Citocina/imunologia , Síndrome da Liberação de Citocina/prevenção & controle , Gerenciamento Clínico , Humanos , Imunidade Inata , Fatores Imunológicos , Inflamação/imunologia , Inflamação/prevenção & controle , SARS-CoV-2 , Vitamina D/uso terapêutico , Zoonoses/imunologia
13.
Proc Natl Acad Sci U S A ; 117(46): 29190-29201, 2020 11 17.
Artigo em Inglês | MEDLINE | ID: mdl-33139552

RESUMO

Nipah virus (NiV) is an emerging bat-borne zoonotic virus that causes near-annual outbreaks of fatal encephalitis in South Asia-one of the most populous regions on Earth. In Bangladesh, infection occurs when people drink date-palm sap contaminated with bat excreta. Outbreaks are sporadic, and the influence of viral dynamics in bats on their temporal and spatial distribution is poorly understood. We analyzed data on host ecology, molecular epidemiology, serological dynamics, and viral genetics to characterize spatiotemporal patterns of NiV dynamics in its wildlife reservoir, Pteropus medius bats, in Bangladesh. We found that NiV transmission occurred throughout the country and throughout the year. Model results indicated that local transmission dynamics were modulated by density-dependent transmission, acquired immunity that is lost over time, and recrudescence. Increased transmission followed multiyear periods of declining seroprevalence due to bat-population turnover and individual loss of humoral immunity. Individual bats had smaller host ranges than other Pteropus species (spp.), although movement data and the discovery of a Malaysia-clade NiV strain in eastern Bangladesh suggest connectivity with bats east of Bangladesh. These data suggest that discrete multiannual local epizootics in bat populations contribute to the sporadic nature of NiV outbreaks in South Asia. At the same time, the broad spatial and temporal extent of NiV transmission, including the recent outbreak in Kerala, India, highlights the continued risk of spillover to humans wherever they may interact with pteropid bats and the importance of limiting opportunities for spillover throughout Pteropus's range.


Assuntos
Quirópteros/virologia , Infecções por Henipavirus/epidemiologia , Infecções por Henipavirus/transmissão , Infecções por Henipavirus/veterinária , Infecções por Henipavirus/virologia , Vírus Nipah/classificação , Vírus Nipah/genética , Animais , Ásia , Bangladesh/epidemiologia , Surtos de Doenças , Feminino , Especificidade de Hospedeiro , Humanos , Imunidade , Masculino , Modelos Biológicos , Epidemiologia Molecular , Vírus Nipah/imunologia , Filogenia , Zoonoses/epidemiologia , Zoonoses/imunologia , Zoonoses/transmissão , Zoonoses/virologia
14.
Biomed Res Int ; 2020: 8024763, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32908913

RESUMO

Cystic echinococcosis (CE) is a zoonotic disease caused by Echinococcus granulosus (Eg) infection. Our previous study confirmed that recombinant Eg.P29 (rEg.P29) could protect against echinococcus granulosus secondary infection in sheep and mice. The aim of the study was to investigate the association between immunoprotection of rEg.P29 vaccine and mmu-miR-374b-5p (miR-374b-5p) and study the immunity influence of miR-374b-5p on CD4+ T cells in mice spleen. MiR-374b-5p level was significantly increased after the second-week and the fourth week of vaccination with rEg.P29. Overexpression of miR-374b-5p increased IFN-γ, IL-2, IL-17A mRNA levels and decreased IL-10 mRNA levels in CD4+ T cells. Moreover, the inhibition of miR-374b-5p decreased IFN-γ and IL-17A and increased IL-10 mRNA levels in CD4+ T cells; this was further confirmed by the flow cytometry. The vaccination of rEg.P29 enhanced miR-374b-5p expression that was associated with a higher Th1 and Th17 immune response, a lower IL-10 mRNA production with miR-374b-5p overexpression, a lower Th1 immune response, and a higher IL-10 mRNA levels with miR-374b-5p inhibitions. To sum up, these data suggest that miR-374b-5p may participate in rEg.P29 immunity by regulating Th1 and Th17 differentiation.


Assuntos
Antígenos de Helmintos/imunologia , Linfócitos T CD4-Positivos/imunologia , Equinococose/imunologia , Echinococcus granulosus/imunologia , MicroRNAs/imunologia , Zoonoses/imunologia , Animais , Antígenos de Helmintos/genética , Linfócitos T CD4-Positivos/parasitologia , Diferenciação Celular/genética , Diferenciação Celular/imunologia , Citocinas/genética , Equinococose/genética , Equinococose/parasitologia , Echinococcus granulosus/genética , Feminino , Proteínas de Helminto/genética , Proteínas de Helminto/imunologia , Humanos , Camundongos , Camundongos Endogâmicos C57BL , MicroRNAs/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ovinos , Células Th1/imunologia , Células Th1/parasitologia , Células Th17/imunologia , Células Th17/parasitologia , Vacinas Sintéticas/genética , Vacinas Sintéticas/imunologia , Zoonoses/genética , Zoonoses/parasitologia
15.
Cell Rep ; 32(2): 107885, 2020 07 14.
Artigo em Inglês | MEDLINE | ID: mdl-32668259

RESUMO

T cell recognition of peptides presented by human leukocyte antigens (HLAs) is mediated by the highly variable T cell receptor (TCR). Despite this built-in TCR variability, individuals can mount immune responses against viral epitopes by using identical or highly related TCRs expressed on CD8+ T cells. Characterization of these TCRs has extended our understanding of the molecular mechanisms that govern the recognition of peptide-HLA. However, few examples exist for CD4+ T cells. Here, we investigate CD4+ T cell responses to the internal proteins of the influenza A virus that correlate with protective immunity. We identify five internal epitopes that are commonly recognized by CD4+ T cells in five HLA-DR1+ subjects and show conservation across viral strains and zoonotic reservoirs. TCR repertoire analysis demonstrates several shared gene usage biases underpinned by complementary biochemical features evident in a structural comparison. These epitopes are attractive targets for vaccination and other T cell therapies.


Assuntos
Linfócitos T CD4-Positivos/imunologia , Epitopos/imunologia , Região Variável de Imunoglobulina/genética , Vírus da Influenza A/imunologia , Adulto , Motivos de Aminoácidos , Sequência de Aminoácidos , Animais , Aves/virologia , Regiões Determinantes de Complementaridade/química , Sequência Conservada , Epitopos/química , Feminino , Células Germinativas/metabolismo , Antígeno HLA-DR1/imunologia , Humanos , Epitopos Imunodominantes/química , Epitopos Imunodominantes/imunologia , Masculino , Pessoa de Meia-Idade , Peptídeos/química , Peptídeos/imunologia , Receptores de Antígenos de Linfócitos T/metabolismo , Suínos/virologia , Doadores de Tecidos , Proteínas Virais/imunologia , Adulto Jovem , Zoonoses/imunologia , Zoonoses/virologia
16.
Arch Med Res ; 51(6): 589-592, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32532524

RESUMO

Coronaviruses recently returned with a new one, SARS-CoV-2, related to a potentially severe respiratory disease-called the coronavirus disease (COVID-19). Research shows that the SARS-CoV-2 can be clustered with the Bat SARS-like coronavirus. Bats possess an additional, innate ability for antiviral defense, and, on the other hand, the potential to go hand-in-hand with the virus to generate variability. Besides the high potential of the novel coronavirus in compromising the respiratory system, its rapid transmission and ability to engage many hosts in severe forms of infections or immunopathological complications make it a tough opponent for the immune system. The interactions between SARS-CoV2 and the host immune system result in unleashing tremendous amounts of cytokines, and these cytokines make a storm that would determine the outcome (recovery or death) of the lungs of the patient.


Assuntos
Betacoronavirus , Infecções por Coronavirus/imunologia , Sistema Imunitário/virologia , Pulmão/virologia , Pneumonia Viral/imunologia , Animais , Antivirais , COVID-19 , Vacinas contra COVID-19 , Quirópteros , Infecções por Coronavirus/prevenção & controle , Infecções por Coronavirus/virologia , Citocinas/imunologia , Epitopos/imunologia , Humanos , Pulmão/imunologia , Pulmão/patologia , Pandemias , Pneumonia Viral/virologia , SARS-CoV-2 , Vacinas Virais , Zoonoses/imunologia
17.
Immunology ; 161(1): 25-27, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32548865

RESUMO

Using the best animal models to study immune responses against specific pathogens or vaccines can dramatically accelerate our understanding. Veterinary species are well studied, particularly livestock, to reduce their disease burden. They have also proven to be powerful models, especially for zoonotic pathogens and novel vaccination strategies. A prerequisite for any model selection is having the right quality and range of species-specific immunological reagents. To help promote the widest possible use of veterinary species, an open access website (https://www.immunologicaltoolbox.co.uk) has been created as a central community annotated hub for veterinary immunological reagents. The website is also the portal into services offered by the UK Immunological Toolbox project that includes antibody generation, sequencing and recombinant expression. The funding for this effort is linked into sustainable sources, but ultimate success relies on community engagement to continually increase the quality and quantity of information. It is hoped that as more users and reagent owners engage, it will become an essential resource for researchers, veterinarians and clinicians alike by removing barriers that prevent the use of the most informative animal models.


Assuntos
Vacinas/imunologia , Medicina Veterinária/métodos , Zoonoses/prevenção & controle , Animais , Desenvolvimento de Medicamentos , Internet , Modelos Animais , Vacinação , Zoonoses/imunologia , Zoonoses/microbiologia
18.
Allergy ; 75(7): 1564-1581, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32396996

RESUMO

As a zoonotic disease that has already spread globally to several million human beings and possibly to domestic and wild animals, eradication of coronavirus disease 2019 (COVID-19) appears practically impossible. There is a pressing need to improve our understanding of the immunology of this disease to contain the pandemic by developing vaccines and medicines for the prevention and treatment of patients. In this review, we aim to improve our understanding on the immune response and immunopathological changes in patients linked to deteriorating clinical conditions such as cytokine storm, acute respiratory distress syndrome, autopsy findings and changes in acute-phase reactants, and serum biochemistry in COVID-19. Similar to many other viral infections, asymptomatic disease is present in a significant but currently unknown fraction of the affected individuals. In the majority of the patients, a 1-week, self-limiting viral respiratory disease typically occurs, which ends with the development of neutralizing antiviral T cell and antibody immunity. The IgM-, IgA-, and IgG-type virus-specific antibodies levels are important measurements to predict population immunity against this disease and whether cross-reactivity with other coronaviruses is taking place. High viral load during the first infection and repeated exposure to virus especially in healthcare workers can be an important factor for severity of disease. It should be noted that many aspects of severe patients are unique to COVID-19 and are rarely observed in other respiratory viral infections, such as severe lymphopenia and eosinopenia, extensive pneumonia and lung tissue damage, a cytokine storm leading to acute respiratory distress syndrome, and multiorgan failure. Lymphopenia causes a defect in antiviral and immune regulatory immunity. At the same time, a cytokine storm starts with extensive activation of cytokine-secreting cells with innate and adaptive immune mechanisms both of which contribute to a poor prognosis. Elevated levels of acute-phase reactants and lymphopenia are early predictors of high disease severity. Prevention of development to severe disease, cytokine storm, acute respiratory distress syndrome, and novel approaches to prevent their development will be main routes for future research areas. As we learn to live amidst the virus, understanding the immunology of the disease can assist in containing the pandemic and in developing vaccines and medicines to prevent and treat individual patients.


Assuntos
Betacoronavirus/imunologia , Infecções por Coronavirus/imunologia , Imunidade Inata , Pneumonia Viral/imunologia , Animais , Anticorpos Antivirais/imunologia , Betacoronavirus/química , COVID-19 , Infecções por Coronavirus/sangue , Infecções por Coronavirus/virologia , Citocinas/imunologia , Eosinófilos/imunologia , Epitopos de Linfócito B/imunologia , Epitopos de Linfócito T/imunologia , Humanos , Linfócitos/imunologia , Linfopenia , Pandemias , Pneumonia Viral/sangue , Pneumonia Viral/virologia , SARS-CoV-2 , Zoonoses/imunologia , Zoonoses/virologia
19.
PLoS One ; 15(4): e0225873, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32352968

RESUMO

Black soldier fly (BSF; Hermetia illucens L.) larvae can convert fresh pig manure into protein and fat-rich biomass, which can then be used as aquafeed for select species. Currently, BSF is the only approved insect for such purposes in Canada, USA, and the European Union. Pig manure could serve as a feed substrate for BSF; however, it is contaminated with zoonotic pathogens (e.g., Staphylococcus aureus and Salmonella spp.). Fortunately, BSF larvae inhibit many of these zoonotic pathogens; however, the mechanisms employed are unclear. We employed RNAi, qRT-PCR, and Illumina MiSeq 16S rDNA high-throughput sequencing to examine the interaction between two immune genes (Duox in Duox-reactive oxygen species [ROS] immune system and TLR3 in the Toll signaling pathway) and select pathogens common in pig manure to decipher the mechanisms resulting in pathogen suppression. Results indicate Bsf Duox-TLR3 RNAi increased bacterial load but decreased relative abundance of Providencia and Dysgonomonas, which are thought to be commensals in the BSF larval gut. Bsf Duox-TLR3 RNAi also inactivated the NF-κB signaling pathway, downregulated the expression of antimicrobial peptides, and diminished inhibitory effects on zoonotic pathogen. The resulting dysbiosis stimulated an immune response by activating BsfDuox and promoting ROS, which regulated the composition and structure of the gut bacterial community. Thus, BsfDuox and BsfTLR3 are important factors in regulating these key gut microbes, while inhibiting target zoonotic pathogens.


Assuntos
Oxidases Duais/imunologia , Microbioma Gastrointestinal , Proteínas de Insetos/imunologia , Esterco/microbiologia , Simuliidae/imunologia , Receptor 3 Toll-Like/imunologia , Animais , Homeostase , Humanos , Larva/imunologia , Larva/microbiologia , Salmonella/imunologia , Infecções por Salmonella/imunologia , Infecções por Salmonella/microbiologia , Transdução de Sinais , Simuliidae/microbiologia , Infecções Estafilocócicas/imunologia , Infecções Estafilocócicas/microbiologia , Staphylococcus aureus/imunologia , Suínos , Zoonoses/imunologia , Zoonoses/microbiologia
20.
Eur J Pharm Sci ; 151: 105387, 2020 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-32454128

RESUMO

The emergence and rapid expansion of the coronavirus disease (COVID-19) require the development of effective countermeasures especially a vaccine to provide active acquired immunity against the virus. This study presented a comprehensive vaccinomics approach applied to the complete protein data published so far in the National Center for Biotechnological Information (NCBI) coronavirus data hub. We identified non-structural protein 8 (Nsp8), 3C-like proteinase, and spike glycoprotein as potential targets for immune responses to COVID-19. Epitopes prediction illustrated both B-cell and T-cell epitopes associated with the mentioned proteins. The shared B and T-cell epitopes: DRDAAMQRK and QARSEDKRA of Nsp8, EDMLNPNYEDL and EFTPFDVVR of 3C-like proteinase, and VNNSYECDIPI of the spike glycoprotein are regions of high potential interest and have a high likelihood of being recognized by the human immune system. The vaccine construct of the epitopes shows stimulation of robust primary immune responses and high level of interferon gamma. Also, the construct has the best conformation with respect to the tested innate immune receptors involving vigorous molecular mechanics and solvation energy. Designing of vaccination strategies that target immune response focusing on these conserved epitopes could generate immunity that not only provide cross protection across Betacoronaviruses but additionally resistant to virus evolution.


Assuntos
Infecções por Coronavirus/imunologia , Infecções por Coronavirus/prevenção & controle , Desenho de Fármacos , Epitopos/imunologia , Pandemias/prevenção & controle , Pneumonia Viral/imunologia , Pneumonia Viral/prevenção & controle , Vacinas Virais/imunologia , Zoonoses/imunologia , Sequência de Aminoácidos , Animais , Linfócitos B/imunologia , COVID-19 , Vacinas contra COVID-19 , RNA-Polimerase RNA-Dependente de Coronavírus , Mapeamento de Epitopos , Glicoproteínas/imunologia , Humanos , Modelos Moleculares , Simulação de Dinâmica Molecular , Receptores Imunológicos/química , Receptores Imunológicos/imunologia , Linfócitos T/imunologia , Proteínas não Estruturais Virais/imunologia , Proteínas Virais/química , Proteínas Virais/imunologia
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