Immunomodulation and Disease Tolerance to Staphylococcus aureus

Abstract

The Gram-positive bacterium Staphylococcus aureus is one of the most frequent pathogens that causes severe morbidity and mortality throughout the world. S. aureus can infect skin and soft tissues or become invasive leading to diseases such as pneumonia, endocarditis, sepsis or toxic shock syndrome. In contrast, S. aureus is also a common commensal microbe and is often part of the human nasal microbiome without causing any apparent disease. In this review, we explore the immunomodulation and disease tolerance mechanisms that promote commensalism to S. aureus.

Keywords: Staphylococcus aureus; disease tolerance; immunomodulation; interleukin-10; microbiome.

Figure 1

The outcome of S. aureus detection depends on the site of infection. In nostrils, macrophages, the primary antigen-presenting cells (APCs), produce high levels of IL-10 upon S. aureus stimulation, which promote commensalism and disease tolerance to S. aureus, and ultimately staphylococcal carriage. Upon cutaneous infection by S. aureus, myeloid-derived suppressor cells (MDSCs) are recruited to the skin and regulate T cell-mediated recall responses, which may facilitate disease tolerance to the microbe. In addition, Langerhans cells are the main APCs in skin, which activate a robust T_H1/T_H17 response, resulting in bacterial clearance. In blood, the primary APCs are monocytes, which produce abundant IL-10 upon staphylococcal infection. This facilitates immune evasion and may lead to sepsis. The human body illustration is from wiseGEEk (http://www.wisegeek.org/how-many-muscles-are-there-in-the-human-body.htm#anatomy-of-human-muscle). DC: dendritic cell; MDSC: myeloid-derived suppressor cell; IL-10: interleukin-10.