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In Situ versus Systemic Immune Response in the Pathogenesis of Cutaneous Leishmaniasis
Augusto M Carvalho1,2,3, Rúbia S Costa1,2, Alexsandro Lago2
1Gonçalo Moniz Institute (IGM), Fiocruz, Salvador 40296-710, BA, Brazil.
Insights
Cytokine profiles in peripheral blood mononuclear cells (PBMCs) do not fully mirror the immune response at cutaneous leishmaniasis (CL) lesion sites. This study highlights distinct immune cell activities in CL patients, impacting disease pathology.
Area of Science:
- Immunology
- Infectious Diseases
Background:
- Cutaneous leishmaniasis (CL) pathogenesis involves immune responses, primarily mediated by blood cells.
- Understanding the correlation between systemic and local immune responses in CL is crucial for effective treatment.
Purpose of the Study:
- To investigate whether cytokine production by peripheral blood mononuclear cells (PBMCs) in CL patients reflects the immune environment at the lesion site.
- To identify key cytokines and their correlations with disease severity.
Main Methods:
- Peripheral blood mononuclear cells (PBMCs) and lesion biopsies from 22 CL patients were stimulated with soluble leishmania antigen (SLA).
- Cytokine levels (TNF, IL-1β, IL-6, IL-17, GzmB, IFN-γ, IL-10) were measured using ELISA.
- Correlations between cytokine levels, lesion size, and patient data were analyzed.
Main Results:
- Cytokine levels for TNF, IL-1β, IL-6, IL-17, and granzyme B (GzmB) were significantly higher in lesion biopsies compared to PBMCs.
- Interferon-gamma (IFN-γ) was higher in PBMCs than in biopsies.
- IL-1β, IL-17, and GzmB showed a strong correlation with lesion size, suggesting their role in CL pathology.
Conclusions:
- The immune response at the CL lesion site differs from that observed in peripheral blood.
- IL-17, in addition to IL-1β and GzmB, plays a significant role in the pathology of CL caused by *Leishmania (Viannia) braziliensis*.
Abstract:
The role of the immune response in the pathogenesis of cutaneous leishmaniasis (CL) due to Leishmania (Viannia) braziliensis is predominantly carried out via blood cells. Here, we evaluate whether cytokine production by peripheral blood mononuclear cells (PBMCs) reflects what has been documented at the lesion site. The participants included 22 CL patients diagnosed with a positive PCR. PBMCs were stimulated for 72 h with a soluble leishmania antigen (SLA). Biopsies obtained from the edge of the ulcers were incubated for the same period. Cytokines in supernatants were assessed via ELISA. TNF, IL-1β, IL-6, IL-17, and granzyme B (GzmB) were higher in the supernatants of biopsies than in PBMCs, but IFN-γ was higher in the supernatants of PBMCs than in biopsies. There was a positive correlation between IFN-γ and TNF in PBMCs, and an inverse correlation between TNF and IL-10 in the cells from the lesion site. A strong correlation between IL-1β, IL-17, and GzmB was observed in the biopsies, and a positive correlation was detected between these cytokines and the lesion size. Our results indicate that the immune response in L. braziliensis lesions is different from that observed in peripheral blood, and our data suggest that in addition to IL-1β and GzmB, IL-17 participates in the pathology of CL.
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