Monócitos inflamatórios na patogênese das lesões teciduais em camundongos infectados por Leishmania major

Abstract

Monocytes are heterogeneous cells and are divided into subpopulations that show variation in size, membrane surface, granularity and nuclear morphology. Components of the mononuclear phagocytic system, monocytes have important functions related to immune responses. Different subpopulations have already been described in several species, with different functions. The classical murine monocytes (Gr1+) show high expression of CCR2, the molecule responsible for the migration of these cells through the CCL2 gradient and have been related to aseptic and infectious inflammatory response. Protozoa of the genus Leishmania are obligate intracellular parasites in mammals, mainly harbored by macrophages. Once infected, macrophages are inactivated, not responding effectively to infection. The resistance to infection observed in C57BL/6 mice has been attributed to the Th1 lymphocyte response due to the production of IFN-γ, stimulating infected macrophages and migrated monocytes to control infection. In mice, monocytes are the first peripheral blood cells to reach the Leishmania major (L. major) infection site, even before the neutrophils arrive. Therefore, the role of the monocyte as an effector cell becomes crucial, both in the appearance of cutaneous lesions and in the resolution of infection. The objective of this work was to evaluate and describe the role of murine monocytes in the kinetics of the formation and resolution of lesion and L. major infection control in C57BL/6 mice, as well as the interaction of these monocytes with infected macrophages. Our results demonstrate that, in vitro, primed-IFN-γ or IFN-γ-treated macrophages have lower resistance to infection than when compared to macrophages treated with IFN-γ-activated monocytes, which in turn are able to induce infected macrophages to death, eliminating permissive host cells and internalized parasites. We also observed that Gr1+ monocytes are the population with the highest number of cells adhered to the infected macrophages, being thus essential for the infection control. CCR2-deficient mice showed a smaller size of lesion, with a similar response to WT, when they receive adoptive transfer of bone marrow cells from WT mice. Our results demonstrate that the migration of Gr1+ monocytes is essential for the control of the infection and also for the appearance and resolution of the lesion.