IL-23 Is Required for Protection against Systemic Infection withListeria monocytogenes

Abstract

Listeria monocytogenes (LM) is a Gram-positive, intracellular bacterium that can induce spontaneous abortion, septicemia, and meningitis. Although it is known that neutrophils are required for elimination of the bacteria and for survival of the host, the mechanisms governing the recruitment of neutrophils to LM-infected tissues are not fully understood. We demonstrate here that IL-23 and the IL-17 receptor A (IL-17RA), which mediates both IL-17A and IL-17F signaling, are necessary for resistance against systemic LM infection. LM-infected IL-23p19 knockout (KO) mice have decreased production of IL-17A and IL-17F, while IFN-γ production is not altered by the lack of IL-23. LM induces the production of IL-17A from γδ T cells, but not CD4, CD8, or NK cells. Furthermore, a lack of efficient neutrophil recruitment to the liver is evident in both IL-23p19 KO and IL-17RA KO mice during LM infection. Immunocytochemical analysis of infected livers revealed that neutrophils were able to localize with LM in IL-23p19 KO and IL-17RA KO mice, indicating that IL-23 and IL-17RA do not regulate the precise localization of neutrophils with LM. The importance of IL-23-induced IL-17A was demonstrated by injecting IL-23p19 KO mice with recombinant IL-17A. These mice had reduced LM bacterial burdens compared with IL-23p19 KO mice that did not receive IL-17A. These results indicate that during LM infection, IL-23 regulates the production of IL-17A and IL-17F from γδ T cells, resulting in optimal liver neutrophil recruitment and enhanced bacterial clearance.

IL‐23 protection against Plasmodium berghei infection in mice is partially dependent on IL‐17 from macrophages

“…A major role for IL-17 is to recruit neutrophils that have protective roles against bacterial infections [10,13]. The number of Gr-1 + cell (mainly neutrophils) in both p19KO and 17KO mice before and after PbNK infection was much less than that observed in WT mice (Supporting Information Fig.…”

“…IL-23-mediated induction of IL-17 from Th17 and γδ T cells activates granulocytes to kill bacteria and fungi [11,12]. In addition, this cytokine restricts the growth of intracellular pathogens in an IL-17-dependent manner [13][14][15]. However, there are only a few reports about whether or not IL-23 plays a protective role against malaria parasites residing in red blood cells (RBCs).…”

“…IL-23-mediated induction of IL-17 from Th17 and γδ T cells activates granulocytes to kill bacteria and fungi [11,12]. In addition, this cytokine restricts the growth of intracellular pathogens in an IL-17-dependent manner [13][14][15]. However, there are only a few reports about whether or not IL-23 plays a protective role against malaria parasites residing in red blood cells (RBCs). IL-12, composed of two heterologous chains (p35 and p40), is known to confer protection against disease as well as causing host pathogenicity during infection with malaria parasites, which can be explained through the activation of IFN-γ-producing Th1 CD4 + T cells [16][17][18].…”

“…Alternatively, liver injury is easily induced in these mice showing higher parasitemia due to attenuated protection because immunopathology is partially dependent on parasite burden [40]. It would be of great interest to investigate these issues in detail.A major role for IL-17 is to recruit neutrophils that have protective roles against bacterial infections [10,13]. The number of Gr-1 + cell (mainly neutrophils) in both p19KO and 17KO mice before and after PbNK infection was much less than that observed in WT mice (Supporting Information Fig.…”

Microparticles released by Listeria monocytogenes-infected macrophages are required for dendritic cell-elicited protective immunity

“…After being engulfed by macrophages, Lm survives by disrupting the phagosomal membrane by secreting virulence factors including listerilysin O, and then escaping into the cytoplasm. In response to Lm, macrophages produce a wide variety of pro-inflammatory cytokines, including TNF-a, IL-1, IL-6, IL-12, IL-23, etc., 2,37,38 which are involved in host defense against this pathogen; however, whether macrophages adapt other pathways involved in the protective immunity remains elusive. The expression of the above cytokines by macrophages is due to recognition of bacterial components or products through pathogen-associated molecule pattern receptors, whose signalings commonly result in the activation of NF-kB and MAPK.…”