TY - JOUR
T1 - Measles virus infection results in suppression of both innate and adaptive immune responses to secondary bacterial infection
AU - Slifka, Mark K.
AU - Homann, Dirk
AU - Tishon, Antoinette
AU - Pagarigan, Robb
AU - Oldstone, Michael B.A.
PY - 2003/3
Y1 - 2003/3
N2 - 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.
AB - 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.
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U2 - 10.1172/JCI13603
DO - 10.1172/JCI13603
M3 - Article
C2 - 12639986
AN - SCOPUS:85047687010
SN - 0021-9738
VL - 111
SP - 805
EP - 810
JO - Journal of Clinical Investigation
JF - Journal of Clinical Investigation
IS - 6
ER -