Immunoregulatory profile of monocytes from cutaneous leishmaniasis patients and association with lesion size.

Leishmaniasis is an important tropical disease composed of several clinical forms that adversely affect millions of people globally. Critical cells involved in the host-Leishmania interaction are monocytes and macrophages, which act to protect against infections due to their ability to both control intracellular infections and regulate the subsequent adaptive immune response. Both soluble factors and cell surface receptors are keys in directing the immune response following interaction with pathogens such as Leishmania. Toll-like receptors (TLRs) have an essential role in immune responses against infections, but little is known about their role in human infection with Leishmania braziliensis. In this work, we evaluated peripheral blood CD14+ monocytes for the expression of immunoregulatory cytokines, co-stimulatory molecules and TLR9 from cutaneous leishmaniasis patients infected with L. braziliensis and noninfected individuals. Our results showed that patients present decreased expression of co-stimulatory molecules such as CD80 and CD86 following culture with media alone or after stimulus with soluble Leishmania antigen. Interestingly, TLR9 expression was higher after culture with soluble Leishmania antigen (SLA), suggesting a role of this molecule in immunoregulation of active disease. Lastly, higher frequencies of TLR9+ monocytes were correlated with greater lesion size. These findings demonstrate a peripheral monocytes profile compatible with important immunoregulatory potential.

Eficácia do óleo de citronela [Cymbopogon nardus (L. ) Rendle] no controle de ectoparasitas de bovinos / Efficacy of citronella [Cymbopogon nardus (L. ) Rendle] oil in the control of bovine ectoparasites

O objetivo desta pesquisa foi avaliar o efeito in vivo do óleo de citronela, no controle do carrapato bovino [Rhipicephalus (Boophilus) microplus], da mosca-dos-chifres (Haematobia irritans), da mosca-dos-estábulos (Stomoxys calcitrans) e da mosca doméstica (Musca domestica). Foram utilizadas 15 vacas da raça Holandês, distribuídas em três grupos de cinco animais cada um. Os tratamentos foram: controle negativo, amitraz a 0,025 por cento e óleo de citronela a 4 por cento. Para avaliação foram contadas fêmeas ingurgitadas de carrapato e moscas antes (média dos dias -3, -2, -1) e após a aplicação dos produtos nos dias 7, 14, 21 e 28; também foram coletadas amostras de sangue. Em 28 dias, houve necessidade de se reaplicar o amitraz e o fitoterápico para controlar a infestação com carrapato. A relação entre o número de aplicações foi de 1:2,5 para o amitraz e o óleo de citronela, respectivamente. A eficácia no controle do carrapato foi de 71,8 e 30,9 por cento para o amitraz e óleo de citronela a 4 por cento, respectivamente, na média pós-tratamento. Verificou-se baixo controle de moscas no tratamento constituído pelo fitoterápico. Não houve diferença entre os tratamentos para os parâmetros sanguíneos.

This study aimed to evaluate the in vivo effect of citronella oil on the control of bovine ticks [Rhipicephalus (Boophilus) microplus], horn flies (Haematobia irritans), stable flies (Stomoxys calcitrans) and houseflies (Musca domestica). Fifteen Holstein cows were allocated to three groups of five animals each. The treatments were: negative control, amitraz at 0.025 percent and citronella oil at 4 percent. Engorged female ticks and flies were counted before (mean of days -3, -2, -1) and at 7, 14, 21 and 28 days after treatment; blood samples were also collected. Within 28 days, amitraz and the phytotherapic agent had to be reapplied to control tick infestation. The relationship among the number of applications was 1:2.5 for amitraz and citronella oil, respectively. The efficacy of tick control was, on average, 71.8 and 30.9 percent for amitraz and citronella oil at 4 percent respectively, post-treatment. Lower control of flies was observed for the phytotherapic group. There was no difference among treatments for blood parameters.

Recruitment of CD8(+) T cells expressing granzyme A is associated with lesion progression in human cutaneous leishmaniasis.

Human infection with Leishmania braziliensis leads to the establishment of cutaneous leishmaniasis (CL), characterized by the appearance of skin lesions that progress from nonulcerated to ulcerated forms. Our goal was to characterize the immunological kinetics associated with this progression, comparing the cellular composition, cytokines and granzyme expression between lesions of patients with early (E-CL) and late stages (L-CL) of CL. Histopathological analysis showed that lesions from L-CL had more exuberant inflammatory infiltrate as compared to E-CL. Although E-CL and L-CL lesions were predominantly mononuclear, lesions from E-CL patients presented higher neutrophil and eosinophil counts than L-CL. While percentages of CD4(+) and of CD68(+) cells were slightly higher in L-CL, a fivefold increase of CD8(+) cells was observed in L-CL, as compared to E-CL. Moreover, CD8(+) T-cells from L-CL expressed significantly higher levels of granzyme A than E-CL. Interestingly, granzyme A expression was positively correlated with intensity of the inflammatory infiltrate in L-CL but not E-CL. Lastly, percentages of IFN-gamma(+) and IL-10(+) cells were higher in L-CL as compared to E-CL, with CD4(+) T-cells and CD68(+) monocytes as the main sources of these cytokines, respectively. These results suggest that recruitment of CD8(+) granzyme A(+) T cells is involved in lesion progression in human CL.

Atypical manifestations of tegumentary leishmaniasis in a transmission area of Leishmania braziliensis in the state of Bahia, Brazil.

American tegumentary leishmaniasis (ATL) can occur in different forms, classically categorised as cutaneous leishmaniasis, mucosal leishmaniasis, diffuse cutaneous leishmaniasis and disseminated leishmaniasis. We analysed the presence of atypical manifestations (vegetative, verrucous, crusted and lupoid) among a cohort of patients presenting to the Health Post of Corte de Pedra, Bahia, Brazil. Among 1396 patients diagnosed with ATL in 2005-2006, 35 patients (2.5%) presented with atypical manifestations of the disease. Of these patients, 14 were pregnant women, 2 were co-infected with HIV and 19 had no co-morbidity or other apparent risk factors for the development of atypical ATL. The latter 19 patients were the focus of this study. They were predominantly adult males, frequently presenting with facial lesions [P<0.001; odds ratio (OR)=17.5, 95% CI 6.1-52.4] and had higher rates of treatment failure with antimonial therapy (P<0.001; OR=327, 95% CI 45-6668) compared with patients with classic ATL attending in the same period. Thirteen cases healed with amphotericin B, introduced after failure of three or more courses of antimony, suggesting that amphotericin B should be considered as the drug of choice for all patients diagnosed with atypical ATL.

Multiclonal Leishmania braziliensis population structure and its clinical implication in a region of endemicity for American tegumentary leishmaniasis.

In Corte de Pedra (CP), northeastern Brazil, Leishmania braziliensis causes three distinct forms of American tegumentary leishmaniasis (ATL). To test the hypothesis that strain polymorphism may be involved in this disease spectrum and accurately characterize the parasite population structure in CP, we compared one L. major, two non-CP L. braziliensis, one CP L. amazonensis, and 45 CP L. braziliensis isolates, obtained over a 10-year period from localized cutaneous, mucosal, and disseminated leishmaniasis patients, with randomly amplified polymorphic DNA (RAPD). Electrophoretic profiles were mostly unique across species. All typing protocols revealed polymorphism among the 45 CP L. braziliensis isolates, which displayed eight different RAPD patterns and greater than 80% overall fingerprint identity, attesting to the adequacy of the tools to assess strain variability in CP's geographically limited population of parasites. The dendrogram based on the sum of RAPD profiles of each isolate unveiled nine discrete typing units clustered into five clades. Global positioning showed extensive overlap of these clades in CP, precluding geographic sequestration as the mechanism of the observed structuralization. Finally, all forms of ATL presented a statistically significant difference in their frequencies among the clades, suggesting that L. braziliensis genotypes may be accompanied by specific disease manifestation after infection.