The extent of monocytic myeloid suppressor cells induction determines the host immune response during Mycobacterium avium infection.

Abstract

Mycobacterium avium is a slow-growing non-tuberculous mycobacterium. While its medical importance is increasing, its virulence is only poorly characterized. A highly virulent M. avium strain ATTC25291 (MAA25291) has been shown to cause severe disease in mice by survival and growth in nitric oxide (NO) producing, immune suppressive monocytic-MDSC (M-MDSC). The induction and persistence of MAA25291 in M-MDSC is still unresolved. In the present study, we were interested in the role of M-MDSC in mice infected with MAA25291 at infection doses that led to the manifestation of clinical disease (high dose) or subclinical disease (low dose). Flow cytometry revealed the presence of M-MDSC in both infection groups, however, this infiltration was significantly lower after low dose infection. Histopathology showed lower infiltration of NOS2 expressing cells in spleen and liver correlated with high CD3T cell numbers after low dose infection, whereas high dose infection of mice led to T cell losses in the tissues. This study highlights that the infection dose significantly affects M-MDSC induction and their immune regulatory roles. Furthermore, it suggests that the induction and persistence of MAA25291 in M-MDSC relies on the amount of NO production.