期刊
CELLULAR IMMUNOLOGY
卷 371, 期 -, 页码 -出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.cellimm.2021.104449
关键词
Visceral leishmaniasis; Leishmania infantum; Neutrophils; IL-32; Immune response
资金
- CAPES, Brazil [001]
- CNPq/FAPEG, Brazil [465771/2014-9-INCT/HPI]
Neutrophils play a crucial role in protecting against visceral leishmaniasis, and IL-32 gamma enhances their recruitment, phagocytosis, and killing of Leishmania parasites. The axis of IL-32 gamma -Th17-neutrophils is vital for controlling VL infection. These findings suggest a potential therapeutic target for enhancing immune response against visceral leishmaniasis.
Neutrophils are important cells in protection against microbial infections including visceral leishmaniasis (VL). It is well known that IL-32 gamma increases the protective T helper 17 cell mediated immune response against Leishmania infantum. Thus, in this study we evaluated whether IL-32 gamma can increase the protective role of neutrophils against VL. In comparison with wild type (WT) mice, transgenic mice for human IL-32 gamma (IL-32 gamma Tg) presented a higher frequency and absolute number of neutrophils in both spleen and liver after the establishment of L. infantum infection. The IL-32 concentrations correlated with neutrophil numbers in the infected tissues. The IL-32 gamma -induced recruitment of neutrophils was dependent on IL-17, since inhibition of Th17 T cells generation and IL17 production with digoxin treatment reversed the effects of IL-32 gamma. In murine neutrophils, the presence of IL-32 gamma enhanced the phagocytosis of L. infantum via CR3. In addition, murine IL-32 gamma Tg neutrophils were able to kill L. infantum due to the increased production of ROS when compared with WT neutrophils. In fact, IL-32 gamma Tg mice lost their ability to control infection by L. infantum when neutrophils were depleted. In parallel, treatment of human neutrophils with recombinant IL-32 gamma increased phagocytosis and ROS-dependent killing of L. infantum, similarly to murine IL-32 gamma Tg neutrophils. The data show that IL-32 gamma induces neutrophil recruitment to organs affected by VL and increases phagocytosis and killing of L. infantum by neutrophils. Together, data indicate the pivotal axis IL-32 gamma -Th17-neutrophils to control VL.
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