Compartmentalized Immune Response in Leishmaniasis: Changing Patterns throughout the Disease

Area of Science:

• Immunology
• Parasitology
• Veterinary Medicine

Background:

• Visceral leishmaniasis (VL) is marked by T-cell unresponsiveness and absent IFN-γ in peripheral blood.
• IFN-γ and TNF-α are upregulated in VL patient tissues and plasma.
• Limited data exists on tissue-specific cytokine profiles and their changes during VL infection.

Purpose of the Study:

• To investigate the mRNA expression of IFN-γ, TNF-α, IL-10, and TGF-β in five target tissues.
• To analyze cytokine profiles at 6 and 16 months post-infection (PI) in a canine VL model.
• To correlate cytokine expression with parasite density and disease progression.

Main Methods:

• Real-time RT-PCR was used to quantify mRNA expression of key cytokines.
• Five target tissues were analyzed in a canine model of experimental Leishmania infantum infection.
• Samples were collected at 6 months and 16 months PI.

Main Results:

• Spleen and liver showed mixed pro- and anti-inflammatory responses with high parasite loads at both time points.
• Popliteal lymph nodes initially upregulated IFN-γ, followed by IL-10 and TGF-β in the chronic phase.
• Skin showed no cytokine response at 6 months PI, but dermal upregulation of all cytokines correlated with parasite growth and clinical disease.

Conclusions:

• Canine VL model reveals central organs (spleen, liver) exhibit mixed immune responses early in infection.
• Peripheral tissues activate anti-inflammatory/regulatory responses in later chronic stages of VL.
• Tissue-specific cytokine dynamics are crucial in understanding VL pathogenesis and progression.