AUTHOR=Reis Natasha Ferraz de Campos , Dupin Talita Vieira , Costa Carolina Rizzaro , Toledo Maytê dos Santos , de Oliveira Vivian Cristina , Popi Ana Flavia , Torrecilhas Ana Claudia , Xander Patricia 

TITLE=Leishmania amazonensis Promastigotes or Extracellular Vesicles Modulate B-1 Cell Activation and Differentiation

JOURNAL=Frontiers in Cellular and Infection Microbiology

VOLUME=10

YEAR=2020

URL=https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2020.573813

DOI=10.3389/fcimb.2020.573813

ISSN=2235-2988

ABSTRACT=<p>B-1 cells are considered an innate-like B cell population that participates in effective innate and adaptive responses to pathogens. B-1 cells produce immunoglobulins, cytokines, chemokines, migrate to inflammatory sites, and differentiate into mononuclear phagocyte-like cells. Murine B-1 cells phagocytosed <italic>Leishmania</italic><italic>in vitro</italic> and <italic>in vivo</italic> and participate in immunity against <italic>Leishmania</italic>. Our group showed that B-1 cells or their extracellular vesicles (EVs) led to a resistance to experimental infection by <italic>L. amazonensis.</italic> However, the B-1 cells’ responses to <italic>Leishmania</italic> or EVs isolated from parasites are still poorly characterized. Studying the activation and differentiation of B-1 cells <italic>in vivo</italic> can contribute to a better understanding of how these cells participate in immunity to <italic>L. amazonensis.</italic> Thus, we evaluated the expression of myeloid (M-csfr, G-csfr, Spi-1) and lymphoid (EBF, E2A, IL-7R) lineage commitment factors, Toll-like receptors (TLRs), activation cell surface markers, nitric oxide (NO) and reactive oxygen species (ROS) production in murine peritoneal B-1 cells collected after 24 or 48 h post-infection with <italic>Leishmania (Leishmania) amazonensis</italic> promastigotes or EVs released by the parasites. Our results demonstrated that <italic>L. amazonensis</italic> infection did not stimulate the expression of CD40, CD80, CD86, F4/80, and MHC II in B-1 cells, but a significant decrease in the production of NO and ROS was observed. The infection induced a significantly higher arginase expression in B-1 cells, but the stimulation with EVs led to a decrease in this gene expression. TLR-2 and TLR-6 had significantly higher expression in B-1 cells from mice intraperitoneally stimulated with the parasite. The TLR-9 expression was higher in animals infected or stimulated for 48 h with EVs. Interestingly, in B-1 cells the stimulus with <italic>L. amazonensis</italic> led to a substantial increase in the expression of myeloid restricted transcription factors. Thus, our study suggests that the parasites or EVs differently modulated the activation and differentiation of B-1 cells.</p>