In vitro initial immune response against Leishmania amazonensis infection is characterized by an increased production of IL-10 and IL-13

Abstract

The initial encounter of Leishmania with its host's immune system is important in the outcome of infection. Previous studies have shown that PBMCs from healthy volunteers (HV) exposed to Leishmania differ in IFN-γ production. We have expanded such observations evaluating the profile and kinetics of cytokines (IFN-γ, IL-12p70, IL-10, IL-13), chemokines (CCL5, CCL3, CCL4, CXCL10), and chemokine receptors (CCR1,CCR5, CXCR3, CCR4) in vitro L. amazonensis-stimulated of HV's PBMCs. HVs were divided in groups of high (HR) or low (LR) IFN-γ responders. In both groups, HR and LR, after L. amazonensis infection there was a predominance of IL-10 and IL-13 over IFN-γ production, while IL-12 was produced in similar amount. Regarding chemokines, a more striking difference was observed for CCL3 expression that was lower at 12 hours and 48 hours post infection in LR than in HR. Interestingly, a downregulation of CCR5 and a greater expression of CCR4 were found in low IFN-γ responders. These data suggest that early after L. amazonensis infection there is a cytokine milieu dominated by IL-13 and IL-10, and despite of this environment, IFN-γ is produced, supporting the complexity of the response. It is noteworthy that the pattern of immune response is mounted in first hours after Leishmania stimulation, with the definition of the differentiation of Th1 versus Th2 cells. It remains to be determined if such an in vitro difference has an in vivo counterpart in terms of susceptibility to infection.

Multifunctional CD4+T cells in patients with American cutaneous leishmaniasis

“…Conversely, it has been demonstrated that LbAg is a more potent stimulator of T cell response than LaAg in individuals infected with L. amazonensis , as well as in individuals infected with parasites from the Viannia subgenus, before and after therapy [49]. It has also been shown that LaAg or live L. amazonensis promastigotes are able to induce high levels of IL‐10 in PBMCs obtained from LaAg‐vaccinated volunteers [50] or from healthy subjects [51], suggesting that the differences observed between LbAg and LaAg stimulation can be related to suppressive factors that are triggered by L. amazonensis parasites. We could not detect CD4 + that were able to produce IL‐10 and IFN‐γ simultaneously and did not observe any differences in the frequency of IL‐10 + CD4 + T cells, or in CD4 + CD25 high IL10 + regulatory T cells between LbAg and LaAg stimulation (data not shown).…”

Gene Expression Profile of High IFN-γ Producers Stimulated with Leishmania braziliensis Identifies Genes Associated with Cutaneous Leishmaniasis

“…Upon stimulation with L . amazonensis , high IFN-γ producers also secrete more TNF [6], more IL-12 and less IL-13 [7]. These results indicate that a low IFN-γ response in vitro accompanies a slower IFN-γ production in vivo and authors suggested that in vitro responses could be used to predict, for example, the pace of post vaccination responses.…”

Olive (Olea europaea) leaf extract alters the cytokine profile of Leishmania major‐infected macrophages: New insight into the underlying mechanism

“…Based on these results, cytokines produced by the immune cells are effective on macrophage physiology and establish three populations of classic, alternative, and regulatory macrophages with different physiologies . Results of the previous studies indicated that in early stages of infection with L. major , macrophages can be activated through the alternative pathway, leading to the up‐regulation of TGFβ gene and arginase 1 enzyme as well as the down‐regulation of TNF‐α . It seems that OLE is able to increase the production of IFNγ and TNFα by activating classic macrophages.…”

“…They justify this finding as follows: In the early hours of infection, the Th 2 response is extremely active and the production of Th 2 ‐dependent cytokines is increased, while the secretion of Th 1 ‐dependent cytokines is decreased. Thus, the parasite survives in the macrophage, leading to the development of disease …”