Mice Mucosal Leishmaniasis model shown high parasite load, increased cytotoxicity and impaired IL-10 + T cell response

Alisson Amaral Da-Rocha¹Julio Souza Dos-Santos²Igor Santos Bittencourt¹Douglas Barroso De-Almeida¹Naiara Carla Santos Manhaes¹Hozany Praxedes¹Joao Victor Paiva Romano²Elias Barbosa Silva-Junior³Antonio Jose Silva-Goncalves⁴Marcia Pereira L Oliveira⁴Luciana P Covre⁵Daniel Claudio Oliveira-Gomes⁵Alda Maria Da-Cruz⁴Alessandra Marcia da Fonseca-Martins⁴Herbert Leonel de Matos Guedes^1,4*

• ¹Instituto de Microbiologia Paulo de Góes, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
• ²Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
• ³Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
• ⁴Instituto Oswaldo Cruz - IOC (FIOCRUZ), Rio de Janeiro, Brazil
• ⁵Universidade Federal do Espirito Santo, Espirito Santo, Brazil

Leishmania infection disease, characterized by the destruction of nasal and oral tissues.The mechanisms by which this disease occurs are still not well understood due to the lack of effective experimental models. Mucosal leishmaniasis is associated with inflammatory response, especially Th17 response. Based on that, in this work, the immunopathological aspects of the experimental infection of BALB/c mice by Leishmania amazonensis in the mucosa site were evaluated due to high susceptibility and the disease been associated with Th17 response. Three infection modes were performed and compared according to the injection site. Six weeks post infection, mice presented edema in the nasal and premaxillary region, with progressive growth until twelve weeks.The micro-Computerized Tomography and the histology images demonstrated that the parasite inoculation led to destruction of squamous and transitional tissues in NC and NB groups, with several cells harboring amastigotes. Mice infected in the mucosa tissues had higher parasite load and IgG, IgM antibody levels and increased production of cytotoxic mediators such as CD107, granzyme b and perforin, inflammatory cytokines as IFN-γ and IL-17, but lower frequencies of CD4 + IL-10 + cells compared to ear dermis.Taken together, our data shows that L. amazonensis parasites are more proliferative in nasal mucosa and the infection leads to an increased inflammatory response compared to ear dermis, pointing out this model as an interesting approach to understand some features of MCL immunopathology.