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 infection alters the recruitment of innate effector cells into the sp...
MV infection alters the recruitment of innate effector cells into the spleen after secondary infection with LM. Mice were either untreated (naive), infected with MV alone, infected with LM alone, or infected with MV and 5 days later coinfected with LM. Cell numbers were quantitated by flow cytometry 8 days after LM infection (i.e., 13 days after MV infection). The total numbers of cells expressing (a) CD11b+ (macrophages), (b) CD11c+ (dendritic cells), (c) DX5+CD3– (NK cells), and (d) Gr-1+CD3– (neutrophils) were calculated per spleen, and the average (± SEM) of four to eight mice per group is shown. Statistical significance was determined using Student’s t test. Equivalent results were observed in two additional experiments.