Differences in the onset of the inflammatory response to cutaneous leishmaniasis in resistant and susceptible mice

Abstract

Sites of cutaneous infection with Leishmania major in genetically susceptible (BALB/c) and resistant (C57B1/6) mice were investigated for the early inflammatory response (6 h to 12 days) by electron microscopy combined with enzyme-histochemical methods. Susceptible BALB/c mice spontaneously recruited only polymorphonuclear leukocytes (PMNs) at the site of infection. Infiltrating mononuclear phagocytes (and eosinophils) were first observed at day 1 in a ratio equal to the influx of PMNs (about 40%). This pattern persisted during the following 11 days of infection. In the resistant C57/B16 mice, the first cellular infiltrate at the infected site contained mononuclear phagocytes (25%) and eosinophils (15%) besides PMNs (60%). Within 3 days after infection, mononuclear phagocytes became the dominant population of cells in cutaneous lesions (up to 80%). It was found in situ that L. major accumulated and replicated in immature macrophages, that is, intermediate stages between monocytes and resident macrophages, which were found in lesions of both strains. The burden of parasites was, however, degraded more rapidly by the infiltrating cells of the resistant mice than by those of the susceptible ones. Within the first 4 days of infection, the parasites were found in PMNs, mononuclear phagocytes, and extracellular spaces in both strains. In susceptible mice this distribution pattern persisted up to 12 days after infection; in resistant C57B1/6 mice parasites accumulated inside mononuclear phagocytes within this period. It is concluded that the features of acute inflammation during leishmaniasis in BALB/c mice are sustained over a prolonged period that is ineffective in the elimination of L. major.

Enhanced Susceptibility toLeishmaniaInfection in Resistant Mice in the Absence of Immediate Early Response Gene X-1

“…Our data suggest that IL-17 secreted by both ␥␦ T cells and Th17 cells can aggravate the inflammation and infection of L. major in the absence of a Th2-skewed immune response. This finding is consistent with the deteriorated role of TGF-␤ in L. major infection, previously demonstrated in various animal models (6,7), and the persistence of neutrophils in susceptible -but not in resistantmouse strains (34). Consistent with the prominent role of IL-17 in neutrophil infiltration (35), a high number of neutrophils was seen in the lesions in IEX-1 KO mice compared with WT mice after infection.…”

MerTK cleavage limits proresolving mediator biosynthesis and exacerbates tissue inflammation

“…Of note, our peritonitis experiments were conducted in C57BL/ 6J mice, with validation using a tissue-injury model and with pathway verification in human macrophages. In contrast, the previous study used BALB/c mice, which are more Th2-dominant, have different responses to both sterile and infectious insults, and demonstrate a less robust capacity to initiate tissue repair (49,50).…”

Leishmania donovani Affects Antigen Presentation of Macrophage by Disrupting Lipid Rafts

“…Although macrophage (M) 4 are generally considered to be the main or only host cells allowing Leishmania to survive and multiply (2), other cells can harbor intact viable parasites at least transiently. For example, Leishmania major parasites have been observed in polymorphonuclear leukocytes, fibroblast, and dendritic cells (DC) at different stages of infection (3). The ability of Langerhans cells and DCs to take up Leishmania is still a matter of debate (4,5).…”