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                  Inflammatory and regulatory immune response in para- kala- azar dermal

                                    leishmaniasis from Maranhão State, Brazil



               Gomes, Cláudia ; Rodrigues, Gabriela ; Souza, Glória ; Braga, Leônidas ; Vasconcelos,
                                 1
                                                        2
                                                                         3
                                                                                             4
               Dewton ; Tomokane, Thayse ; Silva, Renata ; Braz, Lucia ; Laurenti, Márcia ; Lindoso,
                                                                                                  2
                                               2
                                                               5
                                                                              3
                       2
               José Angelo ; Corbett, Carlos ; Gama, Mônica
                                               2
                             6
                                                                4
               1 FMUSP,  LIM-50;  FMUSP/Depto.  Patologia  de  Moléstias  Infecciosas;  USP/  Instituto  de  Medicina
                                                                                  3
                                2
               Tropical;  Universidade Federal do Maranhão;  UNIFESP;  Instituto Emilio Ribas
                        4
                                                                   6
                                                         5

               Visceral leishmaniasis (VL) caused by Leishmania(Leishmania) infantum chagasi is a common disease in
               South America and 90% of cases occur in Brazil. Cutaneous manifestations have been rarely reported and
               may be associated with inadequate immune response to Leishmania and possible genetic predisposition
               of the host. Para-kala-azar dermal leishmaniasis (LDPK) refers to an uncommon cutaneous presentation
               that occurs simultaneously with VL. There is a knowledge gap regarding to immunopathogenesis of LV and
               LDPK; Thus, the present study aimed to evaluate the inflammatory and regulatory immune response in
               cutaneous  lesions  and  systemic  level  (serum)  of  patients  with  LDPK  from  Brazil,  using
               immunohistochemistry and multiplex biomarker assay. An eleven-year-old male patient with a previous
               diagnosis of VL without treatment response developed disseminated cutaneous lesions in the fifth episode
               of relapse. Parasitological diagnosis was positive by myelogram and serological test (rk39). HIV test results
               and  lymphocyte  proliferation  assay  against  specific  stimulus  were  negative.  Lesional  polymorphism
               (erythematous papules, nodules, plaques and infiltration areas) was observed on the face, trunk and limbs.
               Parasites  were  detected  in  the  skin  lesion  by  direct  test  and  histopathological  analysis.  Moderate
               mononuclear inflammatory infiltrate with predominance of richly parasitized vacuolated macrophages were
               observed.  Identification  of L.(L.)infantum  chagasi was  made  by  molecular  tools.  Paraffin-embedded
               biopsies were submitted to immunohistochemistry using markers for CD4, CD8, IL-6, IL-1β, Foxp3, IL-17,
               IL-23, Foxp3; TGF-β and IL-10. The results showed low CD4 and CD8 inflammatory response with alternate
               activation of Th17 cells in situ (IL-17, and discrete participation of regulatory response (Foxp3, IL-10 and
               TGF-β).  Serum  cytokine  analysis  showed  suppression  of  the  systemic  immune  response,  with  low
               production  of  inflammatory  and  regulatory  cytokines.  Our  findings  show  differences  between  local  and
               systemic immune response in PKDL, suggesting a compartmentalization of immune response in this clinical
               presentation  of  the  disease  caused  by L.(L.)infantum  chagasi. Supported  by:  grant#2014/50315-
               0/FAPESP; grant#2016/03165-9/FAPESP; LIM50/HC-FMUSP; UFMA/Maranhão























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