Jaime Zamora-Chimal

Glycine, a non-essential amino acid, plays diverse biological roles, including antimicrobial and anti-inflammatory activities, cytoprotective effects, neurotransmitter functions, and potential anticancer properties. The potential of glycine supplementation in parasitic diseases, such as leishmaniasis, remains underexplored. Leishmania mexicana, a protozoan parasite, is a causative agent of cutaneous leishmaniasis, characterized by chronic lesions and significant immunopathology. This study investigates the impact of glycine supplementation on disease progression and parasite control in a BALB/c mouse model of L. mexicana infection. BALB/c mice were infected with L. mexicana and received glycine-supplemented drinking water ad libitum, beginning on the day of infection. Glycine supplementation exhibited a protective effect, as evidenced by significantly reduced lesion sizes and decreased parasite burdens. Cytokine profiling of spleen cells from glycine-treated mice revealed an immunomodulatory effect, characterized by increased interleukin-10 (IL-10) production and decreased tumor necrosis factor-alpha (TNF-α) levels upon stimulation with L. mexicana promastigote antigens. In vitro studies showed that glycine supplementation inhibited promastigote and amastigote growth in a dose-dependent manner. Macrophages cultured in glycine-enriched media showed reduced parasite recovery from infected macrophages. Importantly, no cytotoxic effects were observed in cultured host cells. Histological analysis of tissue lesions showed a lower parasite burden and diminished inflammatory infiltrate in glycine-treated mice. The histological analysis of liver and kidney tissues from glycine-supplemented mice showed no detectable histopathological alterations in liver or kidney at the tested doses. These findings suggest that glycine may represent a promising anti-Leishmania agent for controlling disease progression. Glycine’s dual ability to modulate host immune responses and directly inhibit parasite growth highlights the potential benefits of early glycine supplementation in cutaneous leishmaniasis.

Leishmania parasites infect mammalian hosts through the bites of sand fly vectors. The response by mast cells (MC) to the parasite and vector-derived factors, delivered by sand fly bites, has not been characterized. We analyzed MC numbers and their mediators in BALB/c mice naturally infected in the ear with Leishmania major through the bite of the sand fly vector Phlebotomus duboscqi and compared them to non-infected sand fly bites. MC were found at the bite sites of infective and non-infected sand flies throughout 48 h, showing the release of granules with intense TNF-α, histamine, and tryptase staining. At 30 min and 48 h, the MC numbers were significantly higher (p < 0.001) in infected as compared to non-infected bites or controls. Neutrophil recruitment was intense during the first 6 h in the skin of infected and non-infected sand fly bites and decreased thereafter. An influx of neutrophils also occurred in lymph nodes, where a strong TNF-α stain was observed in mononuclear cells. Our data show that MC orchestrate an early inflammatory response after infected and non-infected sand fly bites, leading to neutrophilic recruitment, which potentially provides a safe passage for the parasite within the mammalian host.