CD11b+Gr-1low cells that accumulate in M.leprae-induced granulomas of the footpad skin of nude mice have the characteristics of monocytic-myeloid-derived suppressor cells

Abstract

CD11b⁺Gr-1^low cells that are increased in the lungs of a Mycobacterium (M) tuberculosis-infection mouse model have the characteristics of monocytic (M)-myeloid-derived suppressor cells (MDSCs) and harbor M.tuberculosis. Interestingly, a high number of M-MDSCs have also been observed in skin lesions of patients with lepromatous leprosy. We hypothesized that CD11b⁺Gr-1^low cells might be involved in the pathogenesis of leprosy, as they are in tuberculosis. In the current study, we investigated the issue of whether CD11b⁺Gr-1^low cells accumulate in Mycobacterium (M) leprae-induced granulomas of the footpad skin of nude mice. Our results show that CD11b⁺Gr-1^low cells began to accumulate in the 7-month-old M.leprae-induced granulomas and were replaced by other leukocytes, including CD11b⁺Gr-1^high over time during M.leprae infections. CD11b ⁺ Gr-1^low cells expressed the surface markers of M-MDSC, Ly6C^high and Ly6G^low. In addition, CD11b⁺Gr-1^low cells have the nuclei of a mononuclear cell type and expressed higher levels of arginase 1 (Arg1) and inducible NO synthetase (iNOS). Furthermore, they showed a higher infection rate by M.leprae. Taken together, our results indicate that the inoculation with M.leprae induced an accumulation of CD11b ⁺ Gr-1^low at a relatively early stage, 7-month-old M.leprae-induced granulomas, and that CD11b⁺Gr-1^low have the characteristics of M-MDSC and may act as a reservoir for M.leprae.

Keywords: CD11b(+)Gr-1(low); Granuloma; M-MDSCs; Mycobacterium leprae.