Influenza induces GM-CSF deficiency: lung-specific overexpression after infection confers protection (INC1P.355)
Abstract GM-CSF is an essential cytokine for normal lung immune homeostasis. In the current studies we examined the role of GM-CSF and its lung-specific conditional overexpression on the host immune response to influenza. Transgenic tet-GM+/+ mice were intranasally infected with A/PR8/34 H1N1 IAV, B...
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Published in | The Journal of immunology (1950) Vol. 194; no. 1_Supplement; pp. 54 - 54.12 |
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Main Authors | , , , , , , , |
Format | Journal Article |
Language | English |
Published |
01.05.2015
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Online Access | Get full text |
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Summary: | Abstract
GM-CSF is an essential cytokine for normal lung immune homeostasis. In the current studies we examined the role of GM-CSF and its lung-specific conditional overexpression on the host immune response to influenza. Transgenic tet-GM+/+ mice were intranasally infected with A/PR8/34 H1N1 IAV, BALF was collected and single cell lung suspensions were generated using collagenase/DNase digestion. IAV infection induced a prolonged period of GM-CSF deficiency in the lung environment. "Early" (3 days prior to infection) induction of GM-CSF led to protection characterized by significantly enhanced weight recovery as compared to non-induced mice, as well as increased numbers of CD11c+ cells, including CD11b+ and CD11b- dendritic cells as well as enhanced recovery of CD11c+ Siglec-F+ AMs. Interestingly, the weight recovery curves for "late" (3 days post-infection) as compared to "early" GM-CSF overexpression were similar suggesting that GM-CSF may have a role in the resolution of inflammation. Indeed, local GM-CSF restoration caused decreased the frequencies of inflammatory Ly-6C+ monocytes/macrophages and Ly-6G+ neutrophils. Lastly, "late" GM-CSF overexpression accelerated secretion of anti-IAV IgA antibody in BALF. These results indicate viral-induced GM-CSF deficiency impairs recovery from influenza infection, yet can be corrected with exogenous administration of GM-CSF. |
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ISSN: | 0022-1767 1550-6606 |
DOI: | 10.4049/jimmunol.194.Supp.54.12 |