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 r...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.展开更多
基金supported by the National Natural Science Foundation of China(31300143,31570900)the Applied Basic Research Foundation of Yunnan Province,China(2015FB139)the Chinese Academy of Medical Science(CAMS)Innovation Fund for Medical Sciences(2016-I2M-1-014)
文摘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.
