Assuntos
Antivirais/uso terapêutico , Benzimidazóis/administração & dosagem , Fluorenos/administração & dosagem , Infecções por HIV , Hepacivirus , Hepatite C Crônica , Infecções por Parvoviridae , Sofosbuvir/administração & dosagem , Adulto , Coinfecção/diagnóstico , Coinfecção/tratamento farmacológico , Coinfecção/imunologia , Feminino , Infecções por HIV/diagnóstico , Infecções por HIV/tratamento farmacológico , Hepacivirus/genética , Hepacivirus/isolamento & purificação , Hepatite C Crônica/diagnóstico , Hepatite C Crônica/tratamento farmacológico , Hepatite C Crônica/imunologia , Humanos , Imunocompetência , Cirrose Hepática/diagnóstico por imagem , Cirrose Hepática/etiologia , Testes de Função Hepática/métodos , Infecções por Parvoviridae/sangue , Infecções por Parvoviridae/diagnóstico , Testes Sorológicos/métodos , Resposta Viral Sustentada , Resultado do TratamentoRESUMO
Minority communities have borne the brunt of COVID-19 disease in the United States. Nonwhites have contracted most of the SARS-CoV-2 infections; COVID-19 mortality rates for Black Americans are more than twice those for whites. Given this, studying the most effective ways to prevent and treat SARS-CoV-2 in these populations should be a research priority, particularly with respect to vaccine trials. Federal guidelines from the National Institutes of Health and Food and Drug Administration emphasize the need for inclusion of minority groups in these trials, but none of the publicly available SARS-CoV-2 vaccine trial protocols requires representative sampling of minorities. This piece emphasizes the importance of adequate inclusion of minority communities in SARS-CoV-2 vaccine trials, and the implications of this inclusion for SARS-CoV-2 vaccine distribution.
Assuntos
Vacinas contra COVID-19/imunologia , COVID-19/epidemiologia , COVID-19/prevenção & controle , Ensaios Clínicos como Assunto/organização & administração , Grupos Minoritários , SARS-CoV-2/imunologia , Negro ou Afro-Americano , Ensaios Clínicos como Assunto/normas , Etnicidade/estatística & dados numéricos , Disparidades em Assistência à Saúde , Hispânico ou Latino , Humanos , Projetos de Pesquisa , Estados Unidos/epidemiologia , Indígena Americano ou Nativo do AlascaRESUMO
In humans, immunity to Plasmodium sp. generally takes the form of protection from symptomatic malaria (i.e., 'clinical immunity') rather than infection ('sterilizing immunity'). In contrast, mice infected with Plasmodium develop sterilizing immunity, hindering progress in understanding the mechanistic basis of clinical immunity. Here we present a novel model in which mice persistently infected with P. chabaudi exhibit limited clinical symptoms despite sustaining patent parasite burdens for many months. Characterization of immune responses in persistently infected mice revealed development of CD4+ T cell exhaustion, increased production of IL-10, and expansion of B cells with an atypical surface phenotype. Additionally, persistently infected mice displayed a dramatic increase in circulating nonclassical monocytes, a phenomenon that we also observed in humans with both chronic Plasmodium exposure and asymptomatic infection. Following pharmacological clearance of infection, previously persistently infected mice could not control a secondary challenge, indicating that persistent infection disrupts the sterilizing immunity that typically develops in mouse models of acute infection. This study establishes an animal model of asymptomatic, persistent Plasmodium infection that recapitulates several central aspects of the immune response in chronically exposed humans. As such, it provides a novel tool for dissection of immune responses that may prevent development of sterilizing immunity and limit pathology during infection.
Assuntos
Modelos Animais de Doenças , Parasitemia/parasitologia , Plasmodium chabaudi/isolamento & purificação , Animais , Criança , Pré-Escolar , Doença Crônica , Humanos , Lactente , Camundongos , Camundongos Endogâmicos C57BLRESUMO
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.