IL-10 Is an Important Mediator of the Enhanced Susceptibility to Pneumococcal Pneumonia after Influenza Infection

Abstract

Secondary pneumococcal pneumonia is a serious complication during and shortly after influenza infection. We established a mouse model to study postinfluenza pneumococcal pneumonia and evaluated the role of IL-10 in host defense against Streptococcus pneumoniae after recovery from influenza infection. C57BL/6 mice were intranasally inoculated with 10 median tissue culture infective doses of influenza A (A/PR/8/34) or PBS (control) on day 0. By day 14 mice had regained their normal body weight and had cleared influenza virus from the lungs, as determined by real-time quantitative PCR. On day 14 after viral infection, mice received 104 CFU of S. pneumoniae (serotype 3) intranasally. Mice recovered from influenza infection were highly susceptible to subsequent pneumococcal pneumonia, as reflected by a 100% lethality on day 3 after bacterial infection, whereas control mice showed 17% lethality on day 3 and 83% lethality on day 6 after pneumococcal infection. Furthermore, 1000-fold higher bacterial counts at 48 h after infection with S. pneumoniae and, particularly, 50-fold higher pulmonary levels of IL-10 were observed in influenza-recovered mice than in control mice. Treatment with an anti-IL-10 mAb 1 h before bacterial inoculation resulted in reduced bacterial outgrowth and markedly reduced lethality during secondary bacterial pneumonia compared with those in IgG1 control mice. In conclusion, mild self-limiting influenza A infection renders normal immunocompetent mice highly susceptible to pneumococcal pneumonia. This increased susceptibility to secondary bacterial pneumonia is at least in part caused by excessive IL-10 production and reduced neutrophil function in the lungs.

Influenza Infection Leads to Increased Susceptibility to Subsequent Bacterial Superinfection by Impairing NK Cell Responses in the Lung

“…Furthermore, to date, NK cells have only been found to contribute to host defense against primary staphylococcal infection (16,34). In contrast, although exaggerated IL-10 responses to streptococcal superinfection in the fluinfected lung was reportedly linked to increased susceptibility (22,35), we did not detect any measurable levels of IL-10 responses to staphylococcal superinfection in the flu-infected lung (data not shown). These contrasting observations may be due to a number of differences between these and our studies including different strains of flu virus and extracellular bacterial species used and different time intervals between prior flu infection and bacterial superinfection.…”

“…Earlier reports suggest that influenza virus can cause epithelial damage and/or surface receptor changes, which may increase bacterial colonization (17,18). In contrast, altered tneutrophil functions and excessive production of immunosuppressive IL-10 have been implicated in flu infection-increased susceptibility to secondary streptococcal infection in the lung (19)(20)(21)(22). Recently, IFN-g-mediated macrophage functional depression (23) or macrophage desensitization to bacterial ligand-triggered TLR signaling (20) was also found to play a role in this process.…”

Disease Severity in Patients with Simultaneous Influenza and Bacterial Pneumonia

“…Synergistic effects between influenza virus and bacteria have been suggested (6)(7)(8)(9) and receptor-mediated pathways and other mechanisms are implicated in lethal synergism (10,11). …”

Additive Inoculation of Influenza Vaccine and 23-Valent Pneumococcal Polysaccharide Vaccine to Prevent Lower Respiratory Tract Infections in Chronic Respiratory Disease Patients

“…In addition, the number of IL-10 that acts to suppress the defensive ability increases and facilitates the penetration of pathogenic bacteria into the human body (4 …”