In this study, MBL WT mice were found to have a more severe disease in terms of greater weight loss and worse lung pathology than MBL KO mice during either pdmH1N1 or H9N2/G1 virus infection. This suggests that MBL may contribute to the disease severity seen in the MBL WT mice. To elucidate the mechanisms, we investigated the immune response, such as production of cytokines and chemokines at various time points during the infection. Most cytokines and chemokines were detected with similar kinetics, with the peak on day 7 following influenza virus infection in both MBL WT and MBL KO mice. These data suggest that the most critical phase of influenza infection occurs around day 7 after infection, and this is Interestingly, we found that MBL contributed to a more severe proinflammatory response by increasing the production of several proinflammatory cytokines, such as IL-1a, IL-1b, IL-6, TNF-a, and IFN-c. Interleukin 1a and IL-1b are multifunctional proinflammatory cytokines produced readily by influenzainfected leukocytes. They are capable of inducing fever, anorexia, and weight loss [32] . Enhanced production of these cytokines can contribute to the acute lung immunopathology after influenza virus infection in mice [33] and induce gene expression of other cytokines like IL-6 and TNF-a [34, 35] . Despite the abundance of IL-6 following the influenza virus infection, in vivo studies showed that it does not contribute significantly to the pathogenesis of influenza virus infection because the mortality and morbidity observed in mice infected with H5N1 are comparable in both MBL WT and IL-6 deficient mice [36, 37] . Tumor necrosis factor a is readily produced by influenza virusinfected leukocytes and can activate macrophages, stimulate dendritic cell maturation and neutrophils, further enhance the inflammatory response, and activate efficient antigen presentation system in the infected site [20, 38] . Excessive production of TNF-a causes tissue injury, hemorrhagic shock, and death in mice [39, 40] . Interferon c is also an important proinflammatory cytokine that has different functions, including the activation of macrophages, differentiation of Th1 from T cells, enhancement of antigen presentation, and expression of the chemokine gene [41, 42] . These proinflammatory cytokines are commonly found in the acute-phase response to influenza virus infection and may induce immunity but also cause damage to the host tissue [43] . These cytokines were also increased in our infected murine lung, with significantly higher levels in MBL WT mice than in MBL KO mice on day 7, coinciding with body weight loss and lung histological findings. Interleukin 10, an antiinflammatory cytokine, was also significantly higher in MBL WT mice than in MBL KO mice on day 7. Interleukin 10 deficiency was reportedly protective in high-dose influenza virus infection [44] , implying that increased IL-10 may be deleterious to the host. As a consequence of such an overwhelming ''cytokine storm'' [45, 46] , the MBL WT mice were found to have a worse disease course than in the MBL KO mice, including greater body weight loss and more severe lung inflammation.