IL‐17A/F in Leishmania major‐resistant C57BL/6 mice

Abstract

Proinflammatory IL‐17 plays an important role in various diseases and defence against extracellular microorganisms. Healing of leishmaniasis is promoted by Th1/Tc1 cells, whereas Th2/Treg are associated with worsened disease outcome. In addition, high expression of IL‐17A in Leishmania‐susceptible BALB/c and artificial overexpression of IL‐17A in T cells in resistant C57BL/6 mice worsened disease outcome. Since C57BL/6 mice lacking only IL‐17A exhibited no phenotype, and IL‐17A and IL‐17F share similar receptors, but differentially regulate chemokine secretion, we studied mice lacking both IL‐17A and IL‐17F (IL‐17A/F−/−) in infections with Leishmania major. Interestingly, lesion volumes and parasite burdens were comparable to controls, IL‐17A/F−/− mice developed a Th1/Tc1 phenotype, and exhibited normal lesion resolution. Thus, in C57BL/6 mice, secretion of IL‐17A and IL‐17F does not influence disease progression. It appears that—depending on the genetic background—cytokines of the IL‐17 family might be responsible for disease progression primarily in susceptible mice.

Mast Cell Deficiency Protects Susceptible BALB/c Mice from Progressive Murine Cutaneous Leishmaniasis

“…Our findings are thus in line with prior observations in C57BL/6 mice showing that MCprimed dendritic cells induced higher frequencies of IL-17Aeproducing Th17 cells (Dudeck et al, 2011). This has a strong effect on pathology in cutaneous leishmaniasis in BALB/c mice because IL-17 induction is highly relevant in leishmaniasis of susceptible BALB/c mice (Dietze-Schwonberg et al, 2018;Lopez Kostka et al, 2009), whereas in C57BL/6 mice, the absence of IL-17A does not affect disease outcome (Dietze-Schwonberg et al, 2019). Only artificial overexpression of IL-17A in CD4 þ T cells of C57BL/6 mice led to disease aggravation (Dietze-Schwonberg et al, 2019); thus, it appears that in Kit W-sh /Kit W-sh mice, MCassociated decreased levels of IFN-g are responsible for the worsening of the disease, whereas in the same mice on BALB/c background, IL-17Aedependent neutrophil recruitment dominates disease outcome.…”

Extracellular Vesicles in Trypanosomatids: Host Cell Communication

“…Of note, while in Reiner's study, this phenomenon was observed in a context where exosomes were used for vaccination first prior to the challenge with promastigotes, Olivier's lab experiments tried to mimic the physiological setup of the sand fly when taking a blood-meal and both exosomes and parasites are simultaneously transferred. Moreover, and according to previous reports, IL-17a is a very powerful signal to recruit neutrophil and to favor cutaneous leishmaniasis development in mouse and human skin pathology (Maurer et al, 2006;Boaventura et al, 2010;Griewank et al, 2014;Dietze-Schwonberg et al, 2019). Markedly, a study from Olivier's laboratory strongly supports that Leishmania EVs concur to neutrophil migration toward the inoculation site (Hassani et al, 2014).…”

IL-8 and IL-23 Levels in Peripheral Blood Mononuclear Cells of Patients with Cutaneous Leishmaniasis Caused by Leishmania major: A Case-Control Study

“…In C57BL/6 mice, the secretion of IL-17A and IL-17F does not influence the disease progression. It appears that, depending on the genetic background, cytokines of the IL-17 family might be responsible for disease progression primarily in susceptible mice (13). IL-23 stimulated IL-17 production following disease progression to protect patients against Leishmania infection along with inflammatory responses (8,11).…”