Macrophage Polarization in the Skin Lesion Caused by Neotropical Species of Leishmania sp

Abstract

Macrophages play important roles in the innate and acquired immune responses against Leishmania parasites. Depending on the subset and activation status, macrophages may eliminate intracellular parasites; however, these host cells also can offer a safe environment for Leishmania replication. In this sense, the fate of the parasite may be influenced by the phenotype of the infected macrophage, linked to the subtype of classically activated (M1) or alternatively activated (M2) macrophages. In the present study, M1 and M2 macrophage subsets were analyzed by double-staining immunohistochemistry in skin biopsies from patients with American cutaneous leishmaniasis (ACL) caused by L. (L.) amazonensis, L. (V.) braziliensis, L. (V.) panamensis ,and L. (L.) infantum chagasi. High number of M1 macrophages was detected in nonulcerated cutaneous leishmaniasis (NUCL) caused by L. (L.) infantum chagasi ( M 1 = 112 ± 12 , M 2 = 43 ± 12 cells/mm2). On the other side, high density of M2 macrophages was observed in the skin lesions of patients with anergic diffuse cutaneous leishmaniasis (ADCL) ( M 1 = 195 ± 25 , M 2 = 616 ± 114 ), followed by cases of localized cutaneous leishmaniasis (LCL) caused by L. (L.) amazonensis ( M 1 = 97 ± 24 , M 2 = 219 ± 29 ), L. (V.) panamensis ( M 1 = 71 ± 14 , M 2 = 164 ± 14 ), and L. (V.) braziliensis ( M 1 = 50 ± 13 , M 2 = 53 ± 10 ); however, low density of M2 macrophages was observed in NUCL. The data presented herein show the polarization of macrophages in skin lesions caused by different Leishmania species that may be related with the outcome of the disease.

Echinococcus multilocularis protoscoleces enhance glycolysis to promote M2 Macrophages through PI3K/Akt/mTOR Signaling Pathway

“…In the early stages of parasitic infection, hepatic macrophages were preferentially differentiated into M1 macrophages, and both M1 macrophages and M2 macrophages were signi cantly increased during the mature stage [10,21]. Macrophage polarization could be induced by neotropical Leishmania infection, the level of M1 macrophages increased in nonulcerated cutaneous leishmaniasis, and M2 macrophages signi cantly increased in the skin lesions of patients with anergic diffuse cutaneous leishmaniasis [13]. Macrophages preferentially differentiated into the M1 macrophages during the acute stage of Schistosoma japonicum infection.…”

“…We found large numbers of macrophages gathered around the lesion, but their function was limited. Parasitic infection was closely related to different macrophages polarization types [10,13,21]. In the early stages of parasitic infection, hepatic macrophages were preferentially differentiated into M1 macrophages, and both M1 macrophages and M2 macrophages were signi cantly increased during the mature stage [10,21].…”

“…Macrophages coordinate proin ammatory and anti-in ammatory responses to infection and play an important role in the maintenance of cell homeostasis and repair. Parasitic infection was related to the macrophage polarization patterns [10][11][12][13]. Previous studies have found that numerous macrophages gathered around the lesion in AE patients, but the disease was still getting worse, and both M1 and M2 macrophages were signi cantly higher in close liver issue (CLT) than in distant liver tissue (DLT) from the lesion [12].…”

Recent advances in nanomedicines for regulation of macrophages in wound healing

“…As wounds begin to repair, M2 macrophages are activated by interleukin-4 (IL-4) or IL-13 to generate anti-inflammatory factors, including growth factors, surface markers of scavenger receptors, IL-10, and intracellular arginase-1 (Arg-1) expression [ 49 ]. Later in the proliferation phase, M2 macrophages promote T helper 2 (Th2) responses and the adaptive immune system to provide immunomodulatory control of inflammation, which further enhance angiogenesis, fibroblast proliferation, ECM development, and re-epithelialization in the wound area [ 50 , 51 ]. The M1–M2 transition prevents further damage to the wound site and guarantees the scar-free wound healing in the tissue remodeling phase.…”

Shifting Macrophage Phenotypes in Leishmaniasis

“…Although different species of Leishmania trigger distinct immune responses [12][13][14], seminal work catalyzed advances, by employing the experimental L. major model of CL, where C57BL/6 (B6) and BALB/c mice are, respectively, resistant and susceptible to infection. In B6 mice, the Th1 cytokine interferon-γ (IFN-γ) induces classically activated macrophages (M1), which express induced nitric oxide synthase (iNOS) and produce NO (nitric oxide) to kill L. major parasites [8,[15][16][17].…”