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.

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.