Leishmania braziliensis-reactive T cells are down-regulated in long-term cured cutaneous Leishmaniasis, but the renewal capacity of T effector memory compartments is preserved.

Leishmania (Viannia) braziliensis control and tissue damage relate to the effector immune response, which in turn affects clinical outcome. Leishmania reactive CD4(+) and CD8(+) T cells are expanded in long-term healed cutaneous leishmaniasis (hCL) patients but their functional characteristics remain to be determined. This study investigates antigen-specific recall in long-term healed CL caused by L. braziliensis infection. Healed CL subjects were grouped according to the time elapsed since the end of therapy: less than two years and two to five years. Activation phenotype (CD69(+) or CD25(+)) and subpopulations of memory T cell phenotypes [central memory (Tcm): CD45RO(+) CCR7(+) or effector memory (Tem): CD45RO(+) CCR7(-)] were quantified in ex vivo blood mononuclear cells and after Leishmania antigens stimuli. A reduction in the percentage of activated Leishmania-responder CD4(+) and CD8(+) T cells in hCL was associated with the time elapsed since clinical cure. Percentage of CD69(+) in TCD4(+) and TCD8(+) cells were negatively correlated with IL-10 levels. Ex vivo analyses showed contracted Tem CD4(+) and Tem CD8(+) compartments from hCL with long time elapsed since clinical cure, although renewal of these compartments was observed following in vitro exposure to leishmanial stimuli. Our results show that healed L. braziliensis infected patients exhibit a recall response to Leishmania antigens with evident expansion of effector memory T cells. Regulated leishmanial-specific response seems to emerge only about two years after initial contact with the parasite antigens.

Microbial translocation induces an intense proinflammatory response in patients with visceral leishmaniasis and HIV type 1 coinfection.

BACKGROUND: Leishmania infection is a cofactor in the heightened cellular activation observed in patients with American visceral leishmaniasis and human immunodeficiency virus type 1 (HIV) infection, with or without progression to AIDS (AVL/HIV). Thus, the persistence of a high parasite load despite antileishmanial therapy could be responsible for the continued immune stimulation. METHODS: CD8(+) T cells expressing CD38, parasite load, lipopolysaccharide (LPS), soluble CD14, macrophage migration inhibitory factor (MIF), intestinal fatty acid-binding protein (IFABP), and proinflammatory cytokines (interleukin 1ß, interleukin 6, interleukin 8, interleukin 17, interferon γ, and tumor necrosis factor) were measured in 17 patients with AVL/HIV, 16 with HIV, and 14 healthy subjects (HS). RESULTS: Lower Leishmania parasitemia was observed after antileishmanial and antiretroviral therapies. However, higher levels of CD38(+) on CD8(+) T cells were observed in both clinical phases of leishmaniasis, compared with HIV cases. AVL/HIV and HIV patients showed higher levels of LPS and IFABP than HS. Proinflammatory cytokine levels were significantly augmented in patients with active coinfection, as well as those with remission of Leishmania infection. LPS levels and Leishmania infection were positively correlated with CD38 expression on CD8(+) T cells and with IL-6 and IL-8 levels. CONCLUSIONS: LPS levels along with the immune consequences of Leishmania infection were associated with elevated cellular activation in coinfected patients. As a consequence, secondary chemoprophylaxis for leishmaniasis or even the use of antiinflammatory drugs or antibiotics may be considered for improving the prognosis of AVL/HIV.

Atypical lesions as a sign of cutaneous dissemination of visceral leishmaniasis in a human immunodeficiency virus-positive patient simultaneously infected by two viscerotropic Leishmania species.

Leishmaniasis is considered an emerging opportunistic disease in human immunodeficiency virus (HIV)-infected patients who have considerably variable clinical presentation. We report a patient with visceral leishmaniasis who had unexpected clinical aspects (atypical cutaneous lesions appearing after long-term evidence of visceral parasites). The patient had hepatoesplenomegaly in the absence of fever, but was otherwise generally healthy. The HIV viral load was low despite severe immunossupression (low lymphocyte proliferation and low level of interferon-γ, concomitant with a high lymphocyte activation status). Surprisingly, two Leishmania strains were isolated from his bone marrow (typical L. infantum sequence MON-1, type A) and skin (L. donovani MON-2 sequence); this second strain had not been previously identified in Brazil. The association of visceral leishmaniasis and HIV/acquired immunodeficiency syndrome is a largely unknown disease, particularly in areas in which leishmaniasis is not endemic. Such atypical cases indicate that this disease can be undiagnosed in clinical settings.

High levels of T lymphocyte activation in Leishmania-HIV-1 co-infected individuals despite low HIV viral load.

BACKGROUND: Concomitant infections may influence HIV progression by causing chronic activation leading to decline in T-cell function. In the Americas, visceral (AVL) and tegumentary leishmaniasis (ATL) have emerged as important opportunistic infections in HIV-AIDS patients and both of those diseases have been implicated as potentially important co-factors in disease progression. We investigated whether leishmaniasis increases lymphocyte activation in HIV-1 co-infected patients. This might contribute to impaired cellular immune function. METHODS: To address this issue we analyzed CD4+ T absolute counts and the proportion of CD8+ T cells expressing CD38 in Leishmania/HIV co-infected patients that recovered after anti-leishmanial therapy. RESULTS: We found that, despite clinical remission of leishmaniasis, AVL co-infected patients presented a more severe immunossupression as suggested by CD4+ T cell counts under 200 cells/mm3, differing from ATL/HIV-AIDS cases that tends to show higher lymphocytes levels (over 350 cells/mm3). Furthermore, five out of nine, AVL/HIV-AIDS presented low CD4+ T cell counts in spite of low or undetectable viral load. Expression of CD38 on CD8+ T lymphocytes was significantly higher in AVL or ATL/HIV-AIDS cases compared to HIV/AIDS patients without leishmaniasis or healthy subjects. CONCLUSIONS: Leishmania infection can increase the degree of immune system activation in individuals concomitantly infected with HIV. In addition, AVL/HIV-AIDS patients can present low CD4+ T cell counts and higher proportion of activated T lymphocytes even when HIV viral load is suppressed under HAART. This fact can cause a misinterpretation of these laboratorial markers in co-infected patients.

T cells specific to leishmania and other nonrelated microbial antigens can migrate to human leishmaniasis skin lesions.

Immunopathological studies have contributed to the characterization of in situ inflammatory infiltrates in cutaneous leishmaniasis (CL). However, little is known about the T-cell antigen reactivity of these lesions. Our objective was to analyze the responsiveness of lymphocytes from CL lesions to leishmanial and nonrelated antigens in terms of proliferation and the production of cytokines. Mononuclear cells were extracted from lesions, and blood from CL patients infected with Leishmania (Viannia) braziliensis. Activated cells accounted for 35-45% of lesions T-cell subsets. Elevated levels of C1.7/CD244(+)CD8(+) T cells suggest in situ cytotoxic effector function. Lymphocytes isolated from the leishmaniasis lesions proliferated and produced IFN-gamma in response to leishmanial antigens as well as to irrelevant antigens such as Toxoplasma gondii (Tg). Patients presenting with larger lesions had the highest lymphocyte proliferation indexes. A high frequency of Tg-specific cells was detected in the lesions by limiting dilution assay, similar to the frequency of Leishmania-specific cells. Importantly, Tg-reactive cells were not found in lesions of patients without a history of toxoplasmosis. The proportion of Leishmania-reactive CD4(+) and CD8(+) T cells in the lesions was quite variable. Overall, these data suggest that T cells reactive to nonrelevant antigens can migrate to leishmanial lesions and possibly influence the pathogenesis of the disease.

Leishmania (Viannia) guyanensis induces low immunologic responsiveness in leishmaniasis patients from an endemic area of the Brazilian Amazon Highland.

Cutaneous leishmaniasis caused by Leishmania (Viannia) guyanensis (CL-Lguy) is endemic in the Brazilian Amazon, differing from L. braziliensis infection in clinical, diagnostic, and therapeutic aspects. T-cell reactivity to leishmanial antigens possibly involved in the pathogenesis of CL-Lguy was studied herein. Variable lymphoproliferative responses (LPRs) to Leishmania antigens were found among the 23 studied patients, and 50% of them showed low or no response to these antigens. Active disease was associated with an enrichment of leishmanial-reactive T lymphocytes, mainly TCD4(+). High and low interferon (IFN)-gamma producers were observed. TNF-alpha, interleukin (IL)-10, and IL-5 were consistently detected. CL-Lguy displayed low antibody response in comparison to L. braziliensis patients. CL caused by L. braziliensis presented positive LPRs and higher IFN-gamma production but undetectable IL-5. L. guyanensis seems to induce a down-regulation of the immune system compared with L. braziliensis. This finding could explain some aspects of clinical presentation of CL-Lguy, such as high tissue parasite burden and frequent resistance to therapy.

IFNG +874T/A polymorphism is not associated with American tegumentary leishmaniasis susceptibility but can influence Leishmania induced IFN-gamma production.

BACKGROUND: Interferon-gamma is a key cytokine in the protective responses against intracellular pathogens. A single nucleotide polymorphism (SNP) located in the first intron of the human IFN-gamma gene can putatively influence the secretion of cytokine with an impact on infection outcome as demonstrated for tuberculosis and other complex diseases. Our aim was to investigate the putative association of IFNG+874T/A SNP with American tegumentary leishmaniasis (ATL) and also the influence of this SNP in the secretion of IFN-gamma in vitro. METHODS: Brazilian ATL patients (78 cutaneous, CL, and 58 mucosal leishmaniasis, ML) and 609 healthy volunteers were evaluated. The genotype of +874 region in the IFN-gamma gene was carried out by Amplification Refractory Mutational System (ARMS-PCR). Leishmania-induced IFN-gamma production on peripheral blood mononuclear cell (PBMC) culture supernatants was assessed by ELISA. RESULTS: There are no differences between +874T/A SNP frequency in cases and controls or in ML versus CL patients. Cutaneous leishmaniasis cases exhibiting AA genotype produced lower levels of IFN-gamma than TA/TT genotypes. In mucosal cases, high and low IFN-gamma producers were clearly demonstrated but no differences in the cytokine production was observed among the IFNG +874T or A carriers. CONCLUSION: Our results suggest that +874T/A polymorphism was not associated with either susceptibility or severity to leishmaniasis. Despite this, IFNG +874T/A SNP could be involved in the pathogenesis of leishmaniasis by influencing the amount of cytokine released by CL patients, although it could not prevent disease development. On the other hand, it is possible that in ML cases, other potential polymorphic regulatory genes such as TNF-alpha and IL-10 are also involved thus interfering with IFN-gamma secretion.

Paniculite eosinofílica localizada em conseqüência de injeções intramusculares de composto de antimônio para tratamento de leishmaniose tegumentar americana / Localized eosinophilic panniculitis following intramuscular injection of pentavalent antimonium for treatment of american tegumentary leishmaniasis

Paniculite eosinofílica pode ser desencadeada por muitos fatores; aqui os autores descrevem a síndrome em conseqüência de injeções intramusculares de compostos de antimônio para tratamento de leishmaniose tegumentar americana em três pacientes. Todos eles desenvolveram lesões em placa, profundamente infiltradas, no local da injeção antimonial. A histopatologia mostrou acentuado infiltrado inflamatório da hipoderme com numerosos eosinófilos. O estudo imunológico não demonstrou imunoglobulinas ou frações do complemento nas lesões. O diagnóstico final foi de paniculite eosinofílica ocorrendo como efeito colateral da terapia antimonial. O mecanismo patogênico dessa paniculite não pôde ser definido. As hipóteses sugeridas foram de lesão induzida por fenômeno físico - a pressão exercida pelo volume do líquido injetado - ou de uma reação alérgica ao antimônio.

Zoonotic sporothricosis transmitted by cats in Rio de Janeiro, Brazil. A case report.

Sporotricosis is a ubiquitous mycosis characterized by nodular lesions of the cutaneous or subcutaneous tissues and adjacent lymphatics that usually suppurate and ulcerate. Secondary spread to the articular surface and bone or dissemination to the central nervous system, genitourinary tract or lungs is also possible. All forms of sporothricosis are caused by a single species, Sporothrix schenkii. In the great majority of cases the fungus gains entrance into the body through trauma to the skin with some kind of plant materials such as thorns or splinters. Zoonotic transmission is also possible and several animals are implicated. This kind of transmission is most frequently a professional hazard of people dealing with animals but in some parts of the world, including Rio de Janeiro city and metropolitan region, an increase in transmission by pet cats has been noted. In these cases the infection may be observed in the family environment, an important epidemiological consideration to clinicians.

Leishmanial antigens in the diagnosis of active lesions and ancient scars of American tegumentary leishmaniasis patients

Cutaneous biopsies (n = 94) obtained from 88 patients with American tegumentary leishmaniasis were studied by conventional and immunohistochemical techniques...

An outbreak of american cutaneous leishmaniasis (Leishmania braziliensis braziliensis) in a periurban area of Rio de Janeiro city, Brazil: clinical and epidemiological studies

De julho de 1984 a setembro de 1986, 105 casos de leishmaniose cutânea foram estudados numa localidade situada na imediata vizinhança da área urbanizada da regiäo metropolitana da cidade do Rio de Janeiro. A ocupaçäo do sítio deu-se aproximadamente há 20 anos, mas os primeiros casos foram registrados somente seis meses antes do início de nosso estudo. Os casos eram quase que exclusivamente cutâneos, da forma clínica ulcerada com um e seis meses de evoluçäo. O teste de Montenegro foi positivo em todos os casos e anticorpos antileishmania foram detectados por imunofluorescência indireta em 74,3% dos pacientes. A demonstraçäo do parasito foi obtida em 69,5%. Animais domésticos infectados foram facilmente encontrados: 32% dos cäes examinados e 30,8% dos equinos mostravam presença de leishmânia em lesöes ulceradas. Parasitos isolados, tanto de casos humanos como de cäes e equinos, foram imulogicamente caracterizados e identificados com L. b. braziliensis. Da populaçäo de flebotomíneos encontrados 73% eram de Lutzomyia intermedia capturados principalmente com iscas humanas e de animais domésticos. Nossas observaçöes sugerem que esta é uma área de estabelecimento recente da infecçäo por L. b. braziliensis e que a transmissäo ocorre provavelmente tanto no peridomicílio como no interior das habitaçöes