Article
DC-SIGN Mediates the Interaction Between Neutrophils and Leishmania amazonensis-Infected Dendritic Cells to Promote DC Maturation and Parasite Elimination
Registro en:
TIBURCIO, Rafael et al. DC-SIGN Mediates the Interaction Between Neutrophils and Leishmania amazonensis-Infected Dendritic Cells to Promote DC Maturation and Parasite Elimination. Frontiers in Immunology, 2021.
1664-3224
Autor
Tiburcio, Rafael
Melo, Léon Dimitri
Nunes, Sara
Barbosa, Ana Luísa Augusto
Oliveira, Elaine Carvalho de
Suarez, Martha
Borges, Valéria M.
Tavares, Natalia
Brodskyn, Claudia Ida
Resumen
National Council of Research
(CNPq–Universal) grants 476926/2011-4 for CB and FAPESB
APP0108/2016 for VMB. VMB and CB are senior investigators
from CNPq. The funders had no role in study design, data collection
and analysis, decision to publish, or preparation of the manuscript. 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. Conclusion: Our findings suggest that the engagement of direct contact between PMNs
and L. amazonensis-infected DC via DC-SIGN is required for the production of
inflammatory mediators with subsequent parasite elimination and DC maturation.