Host's immune response in unresponsive and responsive patients with anthroponotic cutaneous leishmaniasis treated by meglumine antimoniate: A case-control study of Th1 and Th2 pathways

Int Immunopharmacol. 2019 Apr:69:321-327. doi: 10.1016/j.intimp.2019.02.008. Epub 2019 Feb 14.

Abstract

The objective of the present study was to compare the host's immune responses between unresponsive and responsive patients with anthroponotic cutaneous leishmaniasis (ACL) treated by meglumine antimoniate. A case-control study was carried out in an endemic focus in Iran. Blood samples were taken from patients and peripheral blood mononuclear cells (PBMCs) were isolated. Two wells were considered for each isolate of unresponsive and responsive patients; one was exposed to L. tropica (Lt-stimulated cells) and the other remained non-exposed (non-stimulated cells). After 24 h of incubation, whole RNA was extracted from each sample. Real-time quantitative PCR was carried out to confirm the differences in expression levels of IL-12 P40, IFN-γ, IL-1β, IL-4 and IL-10 among isolates. Data were analyzed and P < 0.05 was considered to be statistically significant. In our study, Lt-stimulated cells and non-stimulated cells in unresponsive groups demonstrated significantly lower expression levels of IL-1β, IL-12 P40 and IFN-γ genes and higher expression levels of IL-4 and IL-10 genes, compared to Lt-stimulated cells and non-stimulated cells in responsive groups. There was a negative correlation between IL-12 P40 with IL-10 and IL-1β with IL-10 in ACL Lt-stimulated cells in unresponsive group, while a positive correlation between IL-12 P40 with IL-1β and IL-12 P40 with IFN-γ in ACL Lt-stimulated cells in responsive group. Probably, different immune responses caused by various factors play a major role in the pathogenesis and development of unresponsiveness in ACL patients. The profile and timing of cytokine production correlated well with the treatment outcome of Leishmania infection.

Keywords: Anthroponotic cutaneous leishmaniasis; Case-control study; Immune response; Th1 and Th2; Unresponsive patients.

MeSH terms

  • Antiprotozoal Agents / therapeutic use*
  • Case-Control Studies
  • Cells, Cultured
  • Cytokines / genetics
  • Cytokines / metabolism
  • Endemic Diseases
  • Female
  • Gene Expression Regulation
  • Humans
  • Inflammation Mediators / metabolism
  • Iran
  • Leishmania tropica / physiology*
  • Leishmaniasis, Cutaneous / drug therapy*
  • Leukocytes, Mononuclear / drug effects*
  • Leukocytes, Mononuclear / physiology
  • Male
  • Meglumine Antimoniate / therapeutic use*
  • Th1 Cells / immunology
  • Treatment Outcome

Substances

  • Antiprotozoal Agents
  • Cytokines
  • Inflammation Mediators
  • Meglumine Antimoniate