Chemokine and cytokine responses are required for protection of the host against viral infection. However, an exuberant response contributes to the influenza-induced morbidity and mortality, especially in severe pandemic and avian influenza infections [16, 52] . In the current study, PR/8 infection induced an increase in TNF-a and IL-1b, well-known paracrine proinflammatory factors. Therefore, we hypothesized that inhibiting these factors might reduce the influenza-induced-inflammatory response. Since the contemporary virus NY/238 induced a similar cytokine and chemokine response as PR/8, it would be reasonable to expect that the regulation of chemokine and cytokine in contemporary influenza infection might also be similar to PR/8 infection. As shown in Figure 5 , inhibiting TNF and/or IL-1 decreased more than 50% of the PR/8-induced secretion of inflammatory chemokines CXCL8 and CCL5 but did not truly affect type I interferon or CXCL10 response, although we observed a decrease of CXCL10 in the presence of both inhibitors ( Figure 5 ). TNF and IL-1 signaling are known to be regulated by NF-kB and there are several NF-kB binding sites in the promoter of CXCL10 [53] , despite of the fact that CXCL10 is an IFN-induced protein [24] . This may explain why inhibiting both pathways slightly decreased the amount of CXCL10 from infected AM. Our results suggest that short term targeting the critical paracrine factors might be beneficial for controlling the excessive infiltration of inflammatory cells and acute lung injury during pandemic or avian flu infection in vivo. Of course, this would require careful consideration of time and dose so as not to increase secondary bacterial infections. Influenza infection significantly decreased mRNA level of macrophage receptors CLEC7A, MSR1, CD36, and MRC1 ( Figure 6A and Table 2 ). CLEC7A belongs to the C-type lectin family and functions as a PRR that recognizes a variety of beta-1, 3-linked and beta-1, 6-linked glucans from fungi. A decrease of CLEC7A in infected AM suggests that these cells might not efficiently recognize and engulf fungi after influenza infection. As shown in Figure 6B , the uptake of zymosan, a yeast cell wall component containing beta-1-3-glycosolic linkeages, was decreased in a dose-dependent manner in PR/8-infected human AM. This effect was not associated with cell loss or cytopathic effect because we did not observe a significant cytopathic effect ( Figure 3B ) even at a MOI of 1 (data not shown). However, the explanation of the decreased uptake might be more complicated than simply the loss of this receptor. In addition, other macrophage receptors MSR1, MARCO, CD36, as well as mannose receptor MRC1 are important for bacterial and particle uptake [54] [55] [56] . Mice with deletions of MSR1 or CD36 have increased susceptibility to pneumococcal or staphylococcal pneumonia [57] [58] [59] . Although impairment of macrophage phagocytosis of bacteria after influenza in mice is well recognized [60, 61] and secondary bacterial infection after influenza is a common clinical problem, we were not able to detect a significant decrease in uptake of heat-inactivated S. aureus in human AM until 72 hpi, at which time the cytopathic effect was significant. We did not observe a consistent decrease of MSR1 protein by flow cytometry in PR/8-infected AM, which might explain why the infection did not impair the bacterial uptake (data not shown). We were also not able to verify the decrease of mRNA level of MARCO, another important macrophage scavenger receptor for influenza infections in mice and human cells [54, 56, 58, 62] . Nine of 11 donors showed a decrease in mRNA levels of MARCO after infection with PR/8 ( Figure 6A ). Two other donors had an increase in levels of MARCO mRNA. Therefore, changes of bacteria-related receptors in human AM after influenza require additional studies, and there may be variations in response among individuals.