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1.
Nat Immunol ; 25(3): 418-431, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38225437

RESUMO

After a century of using the Bacillus Calmette-Guérin (BCG) vaccine, our understanding of its ability to provide protection against homologous (Mycobacterium tuberculosis) or heterologous (for example, influenza virus) infections remains limited. Here we show that systemic (intravenous) BCG vaccination provides significant protection against subsequent influenza A virus infection in mice. We further demonstrate that the BCG-mediated cross-protection against influenza A virus is largely due to the enrichment of conventional CD4+ effector CX3CR1hi memory αß T cells in the circulation and lung parenchyma. Importantly, pulmonary CX3CR1hi T cells limit early viral infection in an antigen-independent manner via potent interferon-γ production, which subsequently enhances long-term antimicrobial activity of alveolar macrophages. These results offer insight into the unknown mechanism by which BCG has persistently displayed broad protection against non-tuberculosis infections via cross-talk between adaptive and innate memory responses.


Assuntos
Vacina BCG , Vírus da Influenza A , Infecções por Orthomyxoviridae , Animais , Camundongos , Administração Intravenosa , Vacina BCG/imunologia , Células T de Memória , Imunidade Treinada , Vacinação , Infecções por Orthomyxoviridae/imunologia , Infecções por Orthomyxoviridae/prevenção & controle
3.
Sci Adv ; 10(39): eado7087, 2024 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-39331716

RESUMO

Pregnancy is associated with profound changes in immunity. However, pregnancy-related respiratory immune adaptations in response to influenza infection and their impact on disease severity remain unclear. Here, we describe, in a preclinical model of mid-gestation pregnancy, a mechanism of enhanced host defense against influenza A virus (IAV) localized to the nasal cavity that limits viral replication and reduces the magnitude of intrapulmonary immune responses. Consequently, the pregnant mice show reduced pulmonary pathology and preserved airway function after IAV infection. The early restriction of viral replication is independent of type I interferon (IFN) but dependent on increased antimicrobial peptides (AMPs) driven by interleukin-17+ (IL-17+) γδ+ T cells within the nasal passages. This pathway of host defense against IAV infection in the upper airways during pregnancy restricts early viral infection and prevents virus dissemination into the lung supporting maternal fitness.


Assuntos
Vírus da Influenza A , Interferon Tipo I , Interleucina-17 , Mucosa Nasal , Infecções por Orthomyxoviridae , Animais , Feminino , Gravidez , Interleucina-17/metabolismo , Interleucina-17/imunologia , Camundongos , Interferon Tipo I/metabolismo , Interferon Tipo I/imunologia , Infecções por Orthomyxoviridae/imunologia , Infecções por Orthomyxoviridae/virologia , Mucosa Nasal/imunologia , Mucosa Nasal/virologia , Mucosa Nasal/metabolismo , Vírus da Influenza A/imunologia , Receptores de Antígenos de Linfócitos T gama-delta/metabolismo , Receptores de Antígenos de Linfócitos T gama-delta/imunologia , Replicação Viral , Pulmão/imunologia , Pulmão/virologia
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