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                 Characterization of the Th1 7 immune response in human cutaneous lesion

                 caused by Leishmania (Viannia) panamensis in Panama, Central America.



               Gonzalez Carrion, Kadir Amilcar ; Calzada, Jose Eduardo ; Diaz, Rosendo ; Tomokane,
                                                                             2
                                                  1
                                                                                               3
               Thaise ; Gomes, Claudia ; Corbett, Carlos ; Saldaña, Azael ; Laurenti, Márcia
                                          4
                                                            4
                       4
                                                                              5
                                                                                                 4
               1 Universidad  de  Sao  Paulo/Patología-FMUSP,  Instituto  Conmemorativo  Gorgas  de  los  Estudios  de  la
               Salud/Investigación  en  Parasitología;  Instituto  Conmemorativo  Gorgas  de  los  Estudios  de  la
                                                   2
               Salud;  Hospital  Santo  Tomás/  Laboratorio  de  Patología;  Universidad  de  Sao  Paulo/Patología-LIM50-
                      3
                                                                    4
               FMUSP;  Instituto  Conmemorativo  Gorgas  de  los  Estudios  de  la  Salud/Investigación  en  Parastiología,
                        5
               Universidad de Panamá/Microbiología

               Cutaneous  leishmaniasis  (CL)  is  an  endemic  disease  in  Panama,  caused  by Leishmania (Viannia)
               parasites, which are characterized for causing ulcerated lesions on the skin. Th17 cells are known for
               playing an important role in eliminating pathogens that are not adequately destroy by Th1 cells, however,
               Th17 may play an ambiguous role in leishmaniasis disease because in some cases it can help with the
               elimination of the parasites but in others, contributes in the pathogenesis of the disease by exacerbating
               the  lesions  on  the  skin.  Despite  the  increasing  knowledge  of  immunopathological  mechanisms  that
               contribute to disease progression, the role of Th17 during L. (V.) panamensis infection remains unclear. In
               this study we characterize the Th17 immune response in skin lesions of patients with CL caused by L. (V.)
               panamensis to understand the pathogenesis of this specie that is endemic in Panama. Biopsies (n = 46)
               from  panamanian  patients  with  localized  CL  were  collected  and  processed  by  usual  histological
               techniques. L.  (V.)  panamensis infection  was  proven  by  in  vitro  isolation  and  characterization  of  the
               parasites by HSP70-RFLP. In situ Th17 immune response was evaluated by immunohistochemistry using
               anti-CD4, anti- RoRγt, anti-IL17, anti-IL6, anti-IL23 and anti-TGF-β. Quantitative morphometric analysis
               showed that the density of CD4+ cells were 914.5±51.76 cells /mm2, RoRγt+ 229,20±13,49 cells/mm2, IL-
               17+ 859.8±70.66 cells/mm2, IL-6+ 273.2±15.89 cells/mm2, IL-23+ 669.8±34.73 cells/mm2 and TGF-β+
               132.2±9.50 cells/mm2. Positive correlations were found between these markers. Although not significant,
               an inverse correlation was observed between the amastigote forms with the number of RoRγt+ and IL-17+
               cells. These data may suggest that Th17 cells could be helping to eliminate the parasite by the action of
               IL17, but it could also play an important role in the development of the disease pathology in tissue infected
               with L. (V.) panamensis. Supported by SNI-SENACYT, FAPESP 2014/50315-0; 2017/03141-5, CNPq and
               LIM50.























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