RESUMO
Trypanosoma cruzi is a protozoan parasite that infects at least 7 million persons in the world (OMS, 2019). In endemic areas, infection normally occurs by vectorial transmission; however, outside, it normally happens by blood and includes congenital transmission. The persistence of T. cruzi during infection suggests the presence of immune evasion mechanisms and the modulation of the anti-parasite response to a profile incapable of eradicating the parasite. Dendritic cells (DCs) are a heterogeneous population of antigen-presenting cells (APCs) that patrol tissues with a key role in mediating the interface between the innate and adaptive immune response. Previous results from our lab and other groups have demonstrated that T. cruzi modulates the functional properties of DCs, in vitro and in vivo. During vectorial transmission, metacyclic (m) trypomastigotes (Tps) eliminated along with the insect feces reach the mucous membranes or injured skin. When transmission occurs by the hematic route, the parasite stage involved in the infection is the circulating or blood (b) Tp. Here, we studied in vitro the effect of both infective mTp and bTp in two different populations of DCs, bone marrow-derived DCs (BMDCs) and XS106, a cell line derived from epidermal DCs. Results demonstrated that the interaction of both Tps imparts a different effect in the functionality of these two populations of DCs, suggesting that the stage of T. cruzi and DC maturation status could define the immune response from the beginning of the ingress of the parasite, conditioning the course of the infection.
Assuntos
Células Dendríticas/imunologia , Células de Langerhans/imunologia , Trypanosoma cruzi/fisiologia , Animais , Apresentação de Antígeno , Linhagem Celular , Proliferação de Células , Células Dendríticas/metabolismo , Células Dendríticas/parasitologia , Interleucina-10/metabolismo , Células de Langerhans/metabolismo , Células de Langerhans/parasitologia , Camundongos Endogâmicos C3H , Camundongos Endogâmicos C57BL , Linfócitos T/fisiologia , Trypanosoma cruzi/crescimento & desenvolvimento , Trypanosoma cruzi/patogenicidade , Fator de Necrose Tumoral alfa/metabolismoRESUMO
Despite the immunological changes recognized to be produced during Leishmania infection and the central role played by Langerhans cells, it is not known whether Leishmaina lipophosphoglycan, the most abundant glycolipid on the parasite surface, affects the functions of Langerhans cells. Here, we provide evidence that exposure of Langerhans cells to Leishmaina (L.) major lipophosphoglycan has consequences for the expression of surface receptors. Down-regulation of receptors involved in host cell-parasite interaction are observed after 4 h exposure of Langerhans cells to lipophosphoglycan. Many of the changes are also induced in Langerhans cells incubated with L. major-conditioned medium, indicating that the observed effects may be mediated by soluble factors released by the parasite into the culture, as it is the case for the carbohydrate moiety of lipophosphoglycan. Taken together, these results indicate that the changes in surface molecule expression induced by the exposure of Langerhans cells to lipophosphoglycan might reflect changes in their signalling functions from the infected skin.
Assuntos
Antígenos de Superfície/efeitos dos fármacos , Glicoesfingolipídeos/farmacologia , Células de Langerhans/efeitos dos fármacos , Leishmania major/química , Animais , Antígenos de Superfície/imunologia , Citometria de Fluxo , Glicoesfingolipídeos/isolamento & purificação , Células de Langerhans/imunologia , Células de Langerhans/parasitologia , Leishmania major/imunologia , Camundongos , Camundongos Endogâmicos BALB CRESUMO
Two patients with diffuse cutaneous leishmaniasis caused by Leishmania mexicana were treated with two leishmanicidal drugs (pentamidine and allopurinol) combined with recombinant interferon-gamma restoring Th-1 favouring conditions in the patients. Parasites decreased dramatically in the lesions and macrophages diminished concomitantly, while IL-12-producing Langerhans cells and interferon-gamma- producing NK and CD8 + lymphocytes increased in a reciprocal manner. The CD4+/CD8 + ratio in the peripheral blood normalized. During exogenous administration of interferon-gamma the parasites' capacity to inhibit the oxidative burst of the patients' monocytes was abolished. Even though Th-1-favouring conditions were restored, both patients relapsed two months after therapy was discontinued. We conclude that the tendency to develop a disease-promoting Th-2 response in DCL patients is unaffected by, and independent of, parasite numbers. Even though intensive treatment in DCL patients induced Th-1 disease restricting conditions, the disease-promoting immunomodulation of few persistent Leishmania sufficed to revert the immune response.