Measles virus infection results in suppression of both innate and adaptive immune responses to secondary bacterial infection
Mark K. Slifka, … , Robb Pagarigan, Michael B.A. Oldstone
Mark K. Slifka, … , Robb Pagarigan, Michael B.A. Oldstone
Published March 15, 2003
Citation Information: J Clin Invest. 2003;111(6):805-810. https://doi.org/10.1172/JCI13603.
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Article Immunology

Measles virus infection results in suppression of both innate and adaptive immune responses to secondary bacterial infection

Abstract

Among infectious agents, measles virus (MV) remains a scourge responsible for 1 million deaths per year and is a leading cause of childhood deaths in developing countries. Although MV infection itself is not commonly lethal, MV-induced suppression of the immune system results in a greatly increased susceptibility to opportunistic bacterial infections that are largely responsible for the morbidity and mortality associated with this disease. Despite its clinical importance, the underlying mechanisms of MV-induced immunosuppression remain unresolved. To begin to understand the basis of increased susceptibility to bacterial infections during MV infection, we inoculated transgenic mice expressing the MV receptor, CD46, with MV and Listeria monocytogenes. We found that MV-infected mice were more susceptible to infection with Listeria and that this corresponded with significantly decreased numbers of macrophages and neutrophils in the spleen and substantial defects in IFN-γ production by CD4+ T cells. The reduction in CD11b+ macrophages and IFN-γ–producing T cells was due to reduced proliferative expansion and not to enhanced apoptosis or to altered distribution of these cells between spleen, blood, and the lymphatic system. These results document that MV infection can suppress both innate and adaptive immune responses and lead to increased susceptibility to bacterial infection.

Authors

Mark K. Slifka, Dirk Homann, Antoinette Tishon, Robb Pagarigan, Michael B.A. Oldstone

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MV-induced immunosuppression results in reduced proliferative expansion ...
MV-induced immunosuppression results in reduced proliferative expansion of CD11b+ and CD11c+ APCs and CD3+ T cells. Studies were performed using transgenic mice expressing the MV receptor CD46 (7). These mice were infected with MV, LM, or MV and LM and given BrdU from days 4–6 after LM infection (days 9–11 after MV infection) (a–c), or BrdU was administered from days 6–8 after LM infection (d). Spleen cells were stained for CD11b (a), CD11c (b), or CD4 and CD8 (c and d) before permeabilization and staining for BrdU that was incorporated into the DNA of proliferating cells. The results show the average (± SEM) of three mice per group.