Mycobacterium tuberculosis infects one-third of the world's human population. This widespread infection depends on the organism's ability to escape host defenses by gaining entry and surviving inside the macrophage. DNA sequences of M. tuberculosis have been cloned; these confer on a nonpathogenic Escherichia coli strain an ability to invade HeLa cells, augment macrophage phagocytosis, and survive for at least 24 hours inside the human macrophage. This capacity to gain entry into mammalian cells and survive inside the macrophage was localized to two distinct loci on the cloned M. tuberculosis DNA fragment.

Cutaneous leishmaniasis due to Leishmania braziliensis infection is an inflammatory disease in which skin ulcer development is associated with mononuclear cell infiltrate and high levels of inflammatory cytokine production. Recently, NLRP3 inflammasome activation and IL-1β production have been associated with increased pathology in murine cutaneous leishmaniasis. We hypothesized that cutaneous leishmaniasis patients have increased expression of NLRP3, leading to high levels of IL-1β production. In this article we show high production of IL-1β in biopsy samples and Leishmania antigen-stimulated peripheral blood mononuclear cells from patients infected with L. braziliensis and reduced IL-1β levels after cure. IL-1β production positively correlated with the area of necrosis in lesions and duration of the lesions. The main source of IL-1β was intermediate monocytes (CD14CD16). Furthermore, our murine experiments show that IL-1β production in response to L. braziliensis was dependent on NLRP3, caspase-1, and caspase-recruiting domain (ASC). Additionally, we observed an increased expression of the NLRP3 gene in macrophages and the NLRP3 protein in intermediate monocytes from cutaneous leishmaniasis patients. These results identify an important role for human intermediate monocytes in the production of IL-1β, which contributes to the immunopathology observed in cutaneous leishmaniasis patients.

Cutaneous leishmaniasis (CL), characterized by an ulcerated lesion, is the most common clinical form of human leishmaniasis. Before the ulcer develops, patients infected with Leishmania (Viannia) braziliensis present a small papule at the site of the sandfly bite, referred to as early cutaneous leishmaniasis (E-CL). Two to four weeks later the typical ulcer develops, which is considered here as late CL (L-CL). Although there is a great deal known about T-cell responses in patients with L-CL, there is little information about the in situ inflammatory response in E-CL. Histological sections of skin biopsies from 15 E-CL and 28 L-CL patients were stained by hematoxilin and eosin to measure the area infiltrated by cells, as well as tissue necrosis. Leishmania braziliensis amastigotes, CD4+, CD8+, CD20+, and CD68+ cells were identified and quantified by immunohistochemistry. The number of amastigotes in E-CL was higher than in L-CL, and the inflammation area was larger in classical ulcers than in E-CL. There was no relationship between the number of parasites and magnitude of the inflammation area, or with the lesion size. However, there was a direct correlation between the number of macrophages and the lesion size in E-CL, and between the number of macrophages and necrotic area throughout the course of the disease. These positive correlations suggest that macrophages are directly involved in the pathology of L. braziliensis–induced lesions.

Biopsies from human localized cutaneous lesions (LCL n = 7) or disseminated lesions (DL n = 8) cases were characterized according to cellular infiltration, frequency of cytokine (IFN-γ, TNF-α) Cutaneous leishmaniasis is a worldwide disease with severe deformating potential in new world. It affects preferentially young economically active patients representing a large burden to the public health system in developing countries. Protection against all forms of leishmaniasis is dependent on cell-mediated immunity (CMI), but the contribution of some cells and cytokines in human disease deserves further scrutiny.CD8 + T cells have been implicated in protection (Muller et al. 1991) being high IFN-γ producers in a murine model of leishmaniasis (Chan 1993). Their role seems to be more in the secondary than in the primary immune response (Muller et al. 1993(Muller et al. , 1994. On the other hand, the course of leishmaniasis in mice lacking beta 2-microglobulin (beta 2-m) gene did not differ from their wild-type counterparts (Overath & Harbecke 1993, Wang et al. 1993, Huber et al. 1998) lessening a role of antigen presentation by major histocompatibility complex class I (MHC I) molecules. In man, a higher percentage of CD8 + over CD4 + T cells was found in mucocutaneous leishmaniasis (MCL) lesions (Castes & Tapia 1998), compared to localized cutaneous lesions (LCL), although similar distributions of CD4 + and CD8 + in LCL have been reported (Barral et al. 1987, Esterre et al. 1992, Lima et al. 1994. The presence of cytotoxic CD8 + T cells has been reported in peripheral blood of MCL but not in LCL patients (Brodskyn et al. 1997). Expansion of CD8 + T cells occurs in the peripheral blood of individuals vaccinated against leishmaniasis (Mendonça et al. 1995, Gurunathan et al. 2000. Especially, the percentage of activated CD8 + T cells was higher in fast responding than in slow responding volunteers to vaccination (Pompeu et al. 2001).The role of B cells in leishmaniasis is also not clear. High antibody levels are present in the more severe clinical form of the cutaneous disease, namely diffuse cutaneous leishmaniasis (DCL) (Schurr et al. 1986, Mengistu et al. 1990), but B cell depletion does not alter the susceptibility or resistance pattern to Leishmania infection in mice (Babai et al. 1999, Brown & Reiner 1999. It seems that B cells are important to induce anti-Leishmania CD4 + Th1 cells and DTH reaction, in the resistant mouse strain, and take part in the humoral response development in susceptible animals (Scott & Farrell 1982, Scott et al. 1986).Predominance of Th1 cytokines like IFN-γ, IL-12, IL-2 and TNF-α over Th2 cytokines, IL-4, IL-5 IL-10 and TGF-β, is correlated in mice to the resistance profile against Leishmania infection (Belosevic et al. 1989, Chatelain et al. 1992, Lezama-Davila et al. 1992, Barral et al. 1993. Imunological studies in humans demonstrated a combination of Th1 and Th2 cytokines with predominance of Th1 in MCL, Th2 predominate in DCL and predominance of Th1 profile in LCL patients , Castes et...

Mucosal leishmaniasis occurs mainly in areas where Leishmania braziliensis is transmitted. It affects predominantly the nasal mucosa and, in more severe forms, can lead to significant tissue destruction. There is no standard method for grading the severity of disease. We categorised 50 patients with mucosal leishmaniasis according to a proposed clinical staging system. Their age ranged from 10 to 86 y (mean ± SD: 36 ± 16 y) and 43 (86%) patients were male. The different degrees of evolution of mucosal disease, from the initial stage to the more severe long-term cases, enabled mucosal leishmaniasis to be graded into five stages. Stage I is characterised by nodular lesions of the mucosa without ulcerations. Stage II is represented by superficial mucosal ulcerations with concomitant fine granular lesions. Stage III is characterised by deep mucosal ulcerations with granular tissue formation. In stage IV there are irreversible lesions leading to perforation of the cartilaginous nasal septum with necrosis. In stage V the nasal pyramid is compromised with alterations of facial features as a consequence of severe tissue destruction. These stages may be useful in characterising the severity of the lesion and optimising the therapeutic outcome.