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Pulmonary immune cells and inflammatory cytokine dysregulation are associated with mortality of il-1R1^(-/-) mice infected with influenza virus(H1N1)

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Zoological Research 2017年第3期38卷 146-154页

作者： Lei Guo Yan-Cui Wang Jun-Jie Mei Ruo-Tong Ning Jing-Jing Wang Jia-Qi Li Xi Wang Hui-Wen Zheng Hai-Tao Fan Long-Ding Liu Department of Viral Immunology Institute of Medical Biology Chinese Academy of Medical Science and Peking Union Medical College Division of Neonatology Department of Pediatrics Children's Hospital of Philadelphia Perelman School of Medicine University of Pennsylvania

Respirovirus infection can cause viral pneumonia and acute lung injury （ALl）. The interleukin-1 （il-1） family consists of proinflammatory cytokines that play essential roles in regulating immune and inflammatory responses in vivo. il-1 signaling is associated with protection against respiratory influenza virus infection by mediation of the pulmonary anti-viral immune response and inflammation. We analyzed the infiltration lung immune leukocytes and cytokines that contribute to inflammatory lung pathology and mortality of fatal H1N1 virus-infected il-1 receptor 1 （il-1R1） deficient mice. Results showed that early innate immune cells and cytokine/chemokine dysregulation were observed with significantly decreased neutrophil infiltration and il-6, TNF-α, G-CSF, KC, and MIP-2 cytokine levels in the bronchoalveolar lavage fluid of infected il-1R1^-/- mice in comparison with that of wild type infected mice. The adaptive immune response against the H1N1 virus in il-1 R1^-/- mice was impaired with downregulated anti-viral Thl cell, CD8＋ cell, and antibody functions, which contributes to attenuated viral clearance. Histological analysis revealed reduced lung inflammation during early infection but severe lung pathology in late infection in il-1R1^-/- mice compared with that in WT infected mice. Moreover, the infected il-1R1^--/ mice showed markedly reduced neutrophil generation in bone marrow and neutrophil recruitment to the inflamed lung. Together, these results suggest that il-1 signaling is associated with pulmonary anti-influenza immune response and inflammatory lung injury, particularly via the influence on neutrophil mobilization and inflammatory cytokine/chemokine production.

关键词： Influenza Lung inflammation il-1 receptor 1 Neutrophil

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