Role of Macrophage Cytokines in Influenza A Virus lnfections

Involvement of the Mannose Receptor in Infection of Macrophages by Influenza Virus

“…A difference in the substrain of PR8 virus used may in part explain the fact that other researchers studying the interaction of influenza virus with M have not found the infectivity of PR8 virus to be particularly low (31). Another important difference may lie in the M populations used.…”

“…By acting as a "dead end" for the virus, M play an important role in early host defense against influenza virus infection. Furthermore, infection of M leads to the production of proinflammatory cytokines and alpha/beta interferon (IFN-␣/␤), which will further act to limit virus spread (31,32).…”

Viral Infection Causes Rapid Sensitization to Lipopolysaccharide: Central Role of IFN-αβ

“…This assumption is supported by in vitro studies. Thus, Influenza A infected human macrophages have been shown to produce dramatically elevated levels of TNF-␣ when cocultured with LPS, and because infected macrophages produced IFN-␣␤, the authors concluded that priming of infected macrophages by this cytokine preconditioned these cells to respond to LPS (42). Moreover, macrophage-synthesized IFN-␣␤ can augment NO production in an autocrine fashion in cultures stimulated with subactivating doses of LPS (26,42).…”

“…Thus, Influenza A infected human macrophages have been shown to produce dramatically elevated levels of TNF-␣ when cocultured with LPS, and because infected macrophages produced IFN-␣␤, the authors concluded that priming of infected macrophages by this cytokine preconditioned these cells to respond to LPS (42). Moreover, macrophage-synthesized IFN-␣␤ can augment NO production in an autocrine fashion in cultures stimulated with subactivating doses of LPS (26,42). In line with these observations a recent in vivo study has revealed that IFN-␣␤ regulates early NO production in Leishmania major-infected mice and that this effect is important for parasite containment (38).…”

IL-1 produced and released endogenously within human islets inhibits beta cell function.

“…Our findings provide biochemical evidence to support a role for resident macrophages as a potential target for an environmental insult that may trigger the initiation of IDDM in genetically predisposed individuals. Viral infections are known stimuli for macrophage activation and cytokine release (32,33), and cellular damage is one mechanism associated with IL-1 release by macrophages (20,21). In addition, we have shown recently that dsRNA, the active component of a viral infection that stimulates antiviral activities in infected cells, stimulates IL-1 release by mouse macrophages (34).…”