A Cytokine Network Balance Influences the Fate of Leishmania (Viannia) braziliensis Infection in a Cutaneous Leishmaniasis Hamster Model

Abstract

The golden hamster is a suitable model for studying cutaneous leishmaniasis (CL) due to Leishmania (Viannia) braziliensis. Immunopathological mechanisms are well established in the L. (L.) major-mouse model, in which IL-4 instructs a Th2 response towards progressive infection. In the present study, we evaluated the natural history of L. braziliensis infection from its first stages up to lesion establishment, with the aim of identifying immunological parameters associated with the disease outcome and parasitism fate. To this end, hamsters infected with 104, 105, or 106 promastigotes were monitored during the first hours (4h, 24h), early (15 days, 30 days) and late (50 days) post-infection (pi) phases. Cytokines, iNOS and arginase gene expression were quantified in the established lesions by reverse transcription-quantitative PCR. Compared to the 105 or 106 groups, 104 animals presented lower lesions sizes, less tissue damage, and lower IgG levels. Basal gene expression in normal skin was high for TGF-β, and intermediary for TNF, IL-6, and IL-4. At 4hpi, no cytokine induction was observed in the 104 group, while an upregulation of IL-6, IL-10, and IL-4 was observed in the 106 group. At 15dpi, lesion appearance was accompanied by an increased expression of all assessed cytokines, markedly in the 105 and 106 groups. Upregulation of all investigated cytokines was observed in the late phase, although less expressive in the 104 group. IFN-γ was the depending variable influencing tissue damage, while IL-6 was associated to parasite load. The network correlating gene expression and clinical and laboratorial parameters indicated inoculum-independent associations at 15 and 30dpi. A strong positive network correlation was observed in the 104 group, but not in the 105 or 106 groups. In conclusion, IL-4, IL-6, IL-10, and TGF-β are linked o L. braziliensis progression. However, a balanced cytokine network is the key for an immune response able to reduce the ongoing infection and reduce pathological damage.

Centrin-deficient Leishmania mexicana confers protection against Old World visceral leishmaniasis

“…In addition, induction of a Th2 dominant response is responsible for pathogenesis in L. mexicana infection of mice 22 . A similar dominant Th2 response has been shown to play an important role in the pathogenesis of a related New World species, L. braziliensis , in a hamster model 23 . Therefore, it is necessary to develop vaccines that are effective at preventing infections with the New World Leishmania species.…”

Low doses of 3-phenyl-lawsone or meglumine antimoniate delivery by tattooing route are successful in reducing parasite load in cutaneous lesions of Leishmania (Viannia) braziliensis-infected hamsters

“…On the other hand, the local inflammation promoted by tattooing may contribute to the induction of an important immune response mediated by T cells, as observed in studies with DNA tattoo vaccines ( Platteel et al., 2017 ; Fotoran et al., 2020 ; Bakker et al., 2021 ). In studies of the hamster model infected with L. (V.) braziliensis carried out by Ribeiro-Romão and collaborators ( 2014 ) and Paiva and collaborators ( 2021 ), the lower parasite load generates a more benign course of infection, without systemic involvement and associated with the expression of a more balanced cytokine network. Therefore, terapeutic intervention in the early stages of infection, when the immune response is being mounted by the host, may favor the best outcome of the disease.…”

The association between type 2 diabetes and pulmonary cavitation revealed among IGRA-positive tuberculosis patients

“…Another study showed that administering IFN-γ after P. aeruginosa challenge resulted in a significant decrease in macroscopic lung pathology changes ( 36 ). Recent literature suggests that IFN-γ gene expression is positively correlated with skin lesion size in hamsters infected with Leishmania braziliensis ( 37 ). The data reported above indicate that the tissue damage from microbial infection, especially lung damage, is associated with IFN-γ.…”