DC-SIGN Mediates the Interaction Between Neutrophils and Leishmania amazonensis-Infected Dendritic Cells to Promote DC Maturation and Parasite Elimination Rafael Tiburcio 1,2 , Le ´ on Dimitri Melo 1,3 , Sara Nunes 1,2 , Ana Luı ´sa Augusto Barbosa 1 , Elaine Carvalho de Oliveira 1,2 , Martha Suarez 1,2 , Vale ´ ria M. Borges 1,2 , Natalia Tavares 1,2 and Claudia Ida Brodskyn 1,2,3 * 1 Instituto Gonc ¸ alo Moniz, Fundac ¸ ão Oswaldo Cruz, Salvador, Brazil, 2 Faculdade de Medicina da Bahia, Universidade Federal da Bahia, Salvador, Brazil, 3 Instituto de Investigac ¸ ão em Imunologia - Instituto de nacional de cie ˆ ncia e tecnologia (iii-INCT), São Paulo, Brazil Background: Leishmaniasis is a neglected arthropod-borne disease that affects millions of people worldwide. Successful Leishmania infections require the mitigation of immune cell functions leading to parasite survival and proliferation. A large body of evidence highlights the involvement of neutrophils (PMNs) and dendritic cells (DCs) in the establishment of immunological responses against these parasites. However, few studies, contemplate to what extent these cells interact synergistically to constrain Leishmania infection. Objective: We sought to investigate how PMNs and infected DCs interact in an in vitro model of Leishmania amazonensis infection. Material and Methods: Briefly, human PMNs and DCs were purified from the peripheral blood of healthy donors. Next, PMNs were activated with fibronectin and subsequently co-cultured with L. amazonensis-infected DCs. Results: We observed that L. amazonensis-infected DC exhibited lower rates of infection when co-cultivated with either resting or activated PMNs. Surprisingly, we found that the release of neutrophil enzymes was not involved in Leishmania killing. Next, we showed that the interaction between PMNs and infected-DCs was intermediated by DC-SIGN, further suggesting that parasite elimination occurs in a contact-dependent manner. Furthermore, we also observed that TNFa and ROS production was dependent on DC-SIGN-mediated contact, as well as parasite elimination is dependent on TNFa production in the co-culture. Finally, we observed that direct contact between PMNs and DCs are required to restore the expression of DC maturation molecules during L. amazonensis infection. Frontiers in Immunology | www.frontiersin.org November 2021 | Volume 12 | Article 750648 1 Edited by: Wanderley De Souza, Federal University of Rio de Janeiro, Brazil Reviewed by: Dominik Rückerl, The University of Manchester, United Kingdom Diego Luis Costa, Departamento de Bioquímica e Imunologia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Brazil *Correspondence: Claudia Ida Brodskyn brodskyn@bahia.fiocruz.br Specialty section: This article was submitted to Parasite Immunology, a section of the journal Frontiers in Immunology Received: 30 July 2021 Accepted: 18 October 2021 Published: 01 November 2021 Citation: Tiburcio R, Melo LD, Nunes S, Barbosa ALA, de Oliveira EC, Suarez M, Borges VM, Tavares N and Brodskyn CI (2021) DC-SIGN Mediates the Interaction Between Neutrophils and Leishmania amazonensis-Infected Dendritic Cells to Promote DC Maturation and Parasite Elimination. Front. Immunol. 12:750648. doi: 10.3389/fimmu.2021.750648 ORIGINAL RESEARCH published: 01 November 2021 doi: 10.3389/fimmu.2021.750648