Recruited macrophages control dissemination of group A Streptococcus from infected soft tissues

I Mishalian, M Ordan, A Peled, A Maly… - The Journal of …, 2011 - journals.aai.org
I Mishalian, M Ordan, A Peled, A Maly, MB Eichenbaum, M Ravins, T Aychek, S Jung…
The Journal of Immunology, 2011journals.aai.org
Abstract Group A Streptococcus (GAS) causes diverse infections in humans, ranging from
mild to life-threatening invasive diseases, such as necrotizing fasciitis (NF), a rapidly
progressing deep tissue infection. Despite prompt treatments, NF remains a significant
cause of morbidity and mortality, even in previously healthy individuals. The early
recruitment of leukocytes is crucial to the outcome of NF; however, although the role of
polymorphonuclear neutrophils (PMNs) in host defense against NF is well established, the …
Abstract
Group A Streptococcus (GAS) causes diverse infections in humans, ranging from mild to life-threatening invasive diseases, such as necrotizing fasciitis (NF), a rapidly progressing deep tissue infection. Despite prompt treatments, NF remains a significant cause of morbidity and mortality, even in previously healthy individuals. The early recruitment of leukocytes is crucial to the outcome of NF; however, although the role of polymorphonuclear neutrophils (PMNs) in host defense against NF is well established, the role of recruited macrophages remains poorly defined. Using a cutaneous murine model mimicking human NF, we found that mice deficient in TNF-α were highly susceptible to sc infections with GAS, and a paucity of macrophages, but not PMNs, was demonstrated. To test whether the effects of TNF-α on the outcome of infection are mediated by macrophages/monocytes, we systemically depleted C57BL/6 mice of monocytes by pharmacological and genetic approaches. Systemic monocyte depletion substantially increased bacterial dissemination from soft tissues without affecting the number of recruited PMNs or altering the bacterial loads in soft tissues. Enhanced GAS dissemination could be reverted by either iv injection of monocytes or sc administration of peritoneal macrophages. These experiments demonstrated that recruited macrophages play a key role in defense against the extracellular pathogen GAS by limiting its spread from soft tissues.
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