Basic Study
Copyright ©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Biol Chem. May 26, 2017; 8(2): 151-162
Published online May 26, 2017. doi: 10.4331/wjbc.v8.i2.151
B-1 cells modulate the murine macrophage response to Leishmania major infection
Angelica F Arcanjo, Marise P Nunes, Elias B Silva-Junior, Monique Leandro, Juliana Dutra Barbosa da Rocha, Alexandre Morrot, Debora Decote-Ricardo, Celio Geraldo Freire-de-Lima
Angelica F Arcanjo, Elias B Silva-Junior, Monique Leandro, Juliana Dutra Barbosa da Rocha, Celio Geraldo Freire-de-Lima, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902, Brazil
Marise P Nunes, Instituto Oswaldo Cruz, FIOCRUZ, Rio de Janeiro 21040-900, Brazil
Alexandre Morrot, Instituto de Microbiologia Paulo de Góes, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902, Brazil
Debora Decote-Ricardo, Instituto de Veterinária, Universidade Federal Rural do Rio de Janeiro, Seropédica 23897-980, Brazil
Author contributions: Arcanjo FA, Nunes MP, Silva-Junior EB, Leandro M and Rocha JDB conceived and designed the experiments; Nunes MP, Morrot A, Decote-Ricardo D and Freire-de-Lima CG performed the experiments; Morrot A, Decote-Ricardo D and Freire-de-Lima CG analyzed the data; Nunes MP, Morrot A and Decote-Ricardo D contributed reagents/materials/analysis tools; Nunes MP, Decote-Ricardo D and Freire-de-Lima CG wrote the paper; Freire-de-Lima CG and Decote-Ricardo D supervised research.
Institutional review board statement: The Animal Ethics Committee (CEUA) in scientific experimentation at the Health Sciences Center of the Federal University of Rio de Janeiro registered with the National Animal Experiment Control Board (CONCEA) on the process number 01200.001568/2013---87 approved this work.
Institutional animal care and use committee statement: The Animal Ethics Committee (CEUA) in scientific experimentation at the Health Sciences Center of the Federal University of Rio de Janeiro registered with the National Animal Experiment Control Board (CONCEA) on the process number 01200.001568/2013---87 approved this work. Where it is planned to use 100 mice, it was approved by this committee on 10/15/2014 under the reference number 062/14. This approval is valid only for the 100 animals described, by the deadline of 10/23/2017.
Conflict-of-interest statement: The authors have no conflicts of interest to report.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Celio Geraldo Freire-de-Lima, PhD, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, CCS, Bloco G, Room C1-015, Ilha do Fundao, Rio de Janeiro 21941-902, Brazil. celio@biof.ufrj.br
Telephone: +55-21-25626523 Fax: +55-21-22808193
Received: August 27, 2016
Peer-review started: August 29, 2016
First decision: November 17, 2016
Revised: February 20, 2017
Accepted: March 14, 2017
Article in press: March 15, 2017
Published online: May 26, 2017
Processing time: 264 Days and 1.4 Hours
Abstract
AIM

To investigate the modulatory effect of B-1 cells on murine peritoneal macrophages infected with Leishmania major (L. major) in vitro.

METHODS

Peritoneal macrophages obtained from BALB/c and BALB/c XID mice were infected with L. major and cultured in the presence or absence of B-1 cells obtained from wild-type BALB/c mice. Intracellular amastigotes were counted, and interleukin-10 (IL-10) production was quantified in the cellular supernatants using an enzyme-linked immunosorbent assay. The levels of the lipid mediator prostaglandin E2 (PGE2) were determined using a PGE2 enzyme immunoassay kit (Cayman Chemical, Ann Arbor, MI), and the number of lipid bodies was quantified in the cytoplasm of infected macrophages in the presence and absence of B-1 cells. Culturing the cells with selective PGE2-neutralizing drugs inhibited PGE2 production and confirmed the role of this lipid mediator in IL-10 production. In contrast, we demonstrated that B-1 cells derived from IL-10 KO mice did not favor the intracellular growth of L. major.

RESULTS

We report that B-1 cells promote the growth of L. major amastigotes inside peritoneal murine macrophages. We demonstrated that the modulatory effect was independent of physical contact between the cells, suggesting that soluble factor(s) were released into the cultures. We demonstrated in our co-culture system that B-1 cells trigger IL-10 production by L. major-infected macrophages. Furthermore, the increased secretion of IL-10 was attributed to the presence of the lipid mediator PGE2 in supernatants of L. major-infected macrophages. The presence of B-1 cells also favors the production of lipid bodies by infected macrophages. In contrast, we failed to obtain the same effect on parasite replication inside L. major-infected macrophages when the B-1 cells were isolated from IL-10 knockout mice.

CONCLUSION

Our results show that elevated levels of PGE2 and IL-10 produced by B-1 cells increase L. major growth, as indicated by the number of parasites in cell cultures.

Keywords: Leishmania major; Macrophages; B-1 cells; Interleukin-10; Prostaglandin E2; Infection

Core tip:This original manuscript describes the modulatory effect of B-1 cells on Leishmania major-infected macrophages. We demonstrated the participation of soluble mediators in a co-culture system and characterized prostaglandin E2 and interleukin-10 (IL-10) as key factors involved in increased intracellular parasite replication. We also demonstrated that cell-cell contact is not important. The same effect was not observed when we used B-1 cells from IL-10 knockout mice, as no significant difference in parasite multiplication was observed. Thus, the current manuscript may be of interest for scientists working in the fields of immunoparasitology or immunomodulation.