Avalia??o da influ?ncia da infec??o pelas formas tripomastigotas metac?clicas ou sangu?neas do Trypanosoma cruzi nas altera??es imunopatog?nicas no col?n de camundongos infectados pela cepa VL-10.

Programa de P?s-Gradua??o em Ci?ncias Biol?gicas. N?cleo de Pesquisas em Ci?ncias Biol?gicas, Pr?-Reitoria de Pesquisa de P?s Gradua??o, Universidade Federal de Ouro Preto.O Trypanosoma cruzi, agente etiol?gico da doen?a de Chagas, possui em seu ciclo evolutivo duas formas infectivas para os mam?feros ? tripomastigota sangu?nea (TS) e tripomastigota metac?clica (TM), que diferem quanto as mol?culas presentes em sua superf?cie, impactando na intera??o inicial parasito/hospedeiro e influenciando o curso da infec??o. Com o controle da transmiss?o vetorial, que ocorre por formas metac?clicas, em alguns pa?ses end?micos, outras formas de infec??o ganham import?ncia. Nos ?ltimos anos tem sido registrado casos de transmiss?o da doen?a de Chagas em pa?ses n?o-end?micos, onde a transmiss?o ocorre por transfus?o de sangue e/ou doa??o de ?rg?os, provenientes de formas sangu?neas. Dessa maneira, avaliar a influ?ncia da infec??o pelas formas tripomastigotas metac?clicas ou sangu?neas do Trypanosoma cruzi, nas altera??es imunopatol?gicas no sangue e no col?n de camundongos infectados pela cepa VL-10, permitir? uma melhor compreens?o dos mecanismos relacionados ? patog?nese da doen?a de Chagas. Baseado nisso, o objetivo deste trabalho foi avaliar as altera??es relacionadas aos par?metros imunopatog?nicos no c?lon durante as fases aguda e cr?nica da infec??o experimental de camundongos Swiss infectados por formas tripomastigotas metac?clicas (TM) ou sangu?neas (TS) da cepa VL-10 do T. cruzi. Os animais infectados com formas TS apresentaram 100% de sobrevida, enquanto essa porcentagem no grupo TM foi de apenas 52%. Al?m disso, animais infectados com formas TS apresentaram maior ?rea sobre a curva de parasitemia em rela??o ao grupo TM. A an?lise das c?lulas mononucleares do sangue perif?rico demonstrou um aumento no percentual de mon?citos na fase aguda nos animais infectados com formas TM. J? an?lise de linf?citos TCD8+ e linf?citos TCD4+ mostrou que independente da fonte do in?culo, houve um aumento e uma redu??o no percentual dessas c?lulas, respectivamente, sendo estas mais precoce no grupo TM. A quantifica??o da carga parasit?ria tecidual mostrou que no c?lon dos animais infectados com formas TM o n?mero de parasitos foi maior nos dias 7 e 14 ap?s a infec??o em rela??o ao grupo TS. J? no 28, 42 e 180 houve uma invers?o desse perfil, apresentando os animais do grupo TS maior carga parasit?ria nesse ?rg?o quando comparado aos animais do grupo TM. A avalia??o do processo inflamat?rio mostrou que h? um aumento dos n?cleos celulares nos animais infectados com formas TS e TM nos dias 28, 42 e 50 em rela??o ao grupo controle , entretanto, na fase cr?nica da doen?a os animais infectados com formas TS j? apresentavam redu??o do infiltrado inflamat?rio enquanto que nos animais infectados com formas TM foi observado presen?a de processo inflamat?rio em 240 DAI, sendo tamb?m observado aumento da produ??o de citocinas pr?-inflamat?rias nos animais infectados com formas TM nessa fase da doen?a em rela??o ao grupo controle. A avalia??o da denerva??o do plexo mioent?rico demonstrou uma redu??o em ambos os grupos infectados em rela??o controle, sendo que mais precoce no grupo TM. Esses resultados sugerem que a infec??o por formas TM promove um elevado parasitismo na fase aguda, provocando uma exacerbada ativa??o do sistema imune, que pode estar relacionado com uma precoce denerva??o do plexo mioent?rico no c?lon e tamb?m pode ser o respons?vel pela manuten??o do processo inflamat?rio na fase cr?nica da doen?a.Trypanosoma cruzi, etiologic agent of Chagas disease, has in its life cycle two infective forms for mammalian hosts - blood trypomastigote (BT) and metacyclic trypomastigote (MT), that differs as to molecules present on their surface, altering the initial relationship parasite/host and impacting in the course of the infection. With the control of vectorial transmission, that is caused by MT forms in endemic countries, other pathways of infection become important. In the last years has been reported transmission of Chagas disease in non-endemic countries, where transmission occurs by blood transfusion and / or organ donation, thanks to the presence of BT forms. In this sense, to evaluate the influence of infection caused by BT or MT forms of T. cruzi, in the immunopathological changes in the colon of Swiss mice infected by the VL-10 strain of T. cruzi will allow a better understanding of mechanisms related to pathogenesis of the disease. Based on this, this work aimed evaluate immunopathogenic parameters in the colon during acute and chronic phases of experimental infection in Swiss mice infected with BT or MT forms of VL-10 strain of T. cruzi. Animals infected with BT forms showed 100% of survival, while this percentage on MT group was only 52%. Moreover, animals infected with BT forms presented greater parasitemia area under the curve than animals infected with MT forms. Analysis of mononuclear cells in the pheripheral blood showed an increase in the percentage of monocytes in the acute phase in animals infected with MT forms. Analysis of TCD8+ and TCD4+ lymphocytes showed that there was an increase and decrease, respectively, independent of the source of inoculum, being earlier in the animals infected with MT forms. The quantification of parasitic load showed that in the colon of animals infected with MT forms the number of parasites was greater at the days 7th and 14th post infection, in relation to TS group. At the days 28th, 42th and 180th a profile inversion was observed, presenting animals of BT group higher parasitism in this organ when compared with animals infected with MT forms. Inflammatory process evaluation demonstrated that there was an increase in the number on cellular nuclei in the animals infected with BT or MT forms at the days 28th, 42th and 50th post infection in relation to non-infected animals. However, on the chronic phase, animals infected with BT already presented reduction of inflammatory process, while animals infected with MT forms showed inflammatory infiltrate at 240th post infection, as well rise of pro-inflammatory cytokines production when compared with control group. Evaluation of denervation of myenteric plexus showed a reduction in both groups in relation to control, being earlier in MT group. Based on these data, the infection by MT forms leads to a higher tissue parasitism in the acute phase, an exacerbated activation of the immune system, that could be related to an earlier denervation of myenteric plexus and be responsible for the maintenance of the inflammatory process on chronic phase of the disease