Staphylococcus aureus induces expansion of myeloid suppressor cells (MDSC)

LEDO C; MENDOZA BERTELLI A; GOMEZ MI

Congreso; LXII REunión anual de la Sociedad Argentina de Inmunologia SAI; 2014

Systemic infections caused by Staphylococcus aureus are a public health concern due to their high morbidity and mortality. Among them, bacterial sepsis is characterized by an initial period of a large inflammatory response which is followed by a period of immunosuppression in which the highest mortality is observed. Among the biological processes that may be involved in the switch to the immunosuppression phase, recent studies suggest that the accumulation of myeloid suppressor cells (MDSC) in lymphoid organs as well as their presence in circulation may play an important role due to their capacity to suppress T cell responses. Since S. aureusis a potent inducer of TNF-α and IL-6 and considering the relevance of these cytokines in the expansion and activation of MDSC, it is possible to hypothesize that S. aureus could induce the expansion of this myeloid population. To demonstrate this hypothesis, groups of mice were inoculated by intraperitoneal route with a sub-lethal dose (4 x 107 CFU) of S. aureus. The presence of bacteria in blood as well as spleen, lung, liver and kidney colonization were observed until day 8 post-inoculation. A significant increase in the levels of circulating IL-6 was observed at 4 and 6 hours post-inoculation (p<0,0001, Student t Test). A significant increase in the accumulation of MDSC, defined as CD11b+Gr1+, cells was observed in spleen and bone marrow at day 4 post-inoculation (p<0.01, p<0.05) and in the spleen at day 8 post-inoculation (p<0.05) compared to the percentages found in control animals. CD11b+Gr1+ cells were not found in the inguinal lymph nodes at any of the times evaluated. MDSC found in the spleen at day 8 post-inoculation were purified and a heterogeneous population of immature cells with a prevalence of granulocytic morphology was observed by Giemsa staining. The present results demonstrate the ability of S. aureus to promote MDSC expansion during the course of systemic infection.