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Pneumocystis Infection Enhances Antibody-Mediated Resistance to a Subsequent Influenza Infection¹

Department of Veterinary Molecular Biology, Montana State University, Bozeman, MT 59715

In contrast to the detrimental outcomes most often associated with the resolution of coinfections, the model presented here involving a localized Pneumocystis infection of the lung, followed 2 wk later by an influenza virus infection, results in a significant beneficial outcome for the host. In the week following the influenza infection, immunocompetent coinfected animals exhibited an accelerated rate of virus clearance, an accelerated appearance of higher influenza-specific neutralizing Ab titers in their serum and bronchoalveolar lavage fluid (BALF), significantly reduced inflammatory cytokine levels in their BALF, and reduced levels of morbidity relative to animals infected only with influenza virus. The beneficial outcome observed in coinfected immunocompetent animals was dependent on the ongoing resolution of a viable Pneumocystis infection. No differences in viral clearance were detected between coinfected and influenza-only-infected µMT mice or likewise for SCID mice. The accelerated anti-influenza response did not appear to be associated with influenza-specific CD8 T cell-mediated responses or NK cell responses in the lung. Rather, the increased rate of viral clearance was due to the enhancement of the influenza-specific Ab response, which in turn was transiently dependent upon the resolution of the ongoing Pneumocystis infection.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by National Institutes of Health Grants HL55002 and RR020185 (to A.G.H.) and from Idea Network of Biomedical Research Excellence Grant RR16455.

² Address correspondence and reprint requests to Dr. James A. Wiley, Department of Veterinary Molecular Biology, Montana State University, Bozeman, MT 59717. E-mail adddress: jwiley{at}montana.edu

³ Abbreviations used in this paper: BALF, bronchoalveolar lavage fluid; LDH, lactate dehydrogenase; iBALT, inducible BALT.