Complement C5 activation during influenza A infection in mice contributes to neutrophil recruitment and lung injury.

Abstract

Influenza virus A (IAV) causes annual epidemics and intermittent pandemics that affect millions of people worldwide. Potent inflammatory responses are commonly associated with severe cases of IAV infection. The complement system, an important mechanism of innate and humoral immune responses to infections, is activated during primary IAV infection and mediates, in association with natural IgM, viral neutralization by virion aggregation and coating of viral hemmagglutinin. Increased levels of the anaphylatoxin C5a were found in patients fatally infected with the most recent H1N1 pandemic virus. In this study, our aim was to evaluate whether targeting C5 activation alters inflammatory lung injury and viral load in a murine model of IAV infection. To address this question C57Bl/6j mice were infected intranasally with 10(4) PFU of the mouse adapted Influenza A virus A/WSN/33 (H1N1) or inoculated with PBS (Mock). We demonstrated that C5a is increased in bronchoalveolar lavage fluid (BALF) upon experimental IAV infection. To evaluate the role of C5, we used OmCI, a potent arthropod-derived inhibitor of C5 activation that binds to C5 and prevents release of C5a by complement. OmCI was given daily by intraperitoneal injection from the day of IAV infection until day 5. Treatment with OmCI only partially reduced C5a levels in BALF. However, there was significant inhibition of neutrophil and macrophage infiltration in the airways, Neutrophil Extracellular Traps (NETs) formation, death of leukocytes, lung epithelial injury and overall lung damage induced by the infection. There was no effect on viral load. Taken together, these data suggest that targeting C5 activation with OmCI during IAV infection could be a promising approach to reduce excessive inflammatory reactions associated with the severe forms of IAV infections.

• Authors: Cristiana C Garcia, Wynne Weston-Davies, Remo C Russo, Luciana P Tavares, Milene A Rachid, José C Alves-Filho, Alexandre V Machado, Bernhard Ryffel, Miles A Nunn, Mauro M Teixeira
• Journal: PloS one (PLoS One) Vol. 8 Issue 5 Pg. e64443 ( 2013) ISSN: 1932-6203 [Electronic] United States
• PMID: 23696894 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Complement C5

Topics

• Animals
• Complement C5 (metabolism)
• Humans
• Influenza A virus (immunology, pathogenicity)
• Lung Injury (etiology, virology)
• Male
• Mice
• Mice, Inbred C57BL
• Neutrophil Infiltration (physiology)
• Orthomyxoviridae Infections (complications, immunology, virology)