Biology subjects

Dos-Santos, J. S.

Publications and source records attributed to Dos-Santos, J. S..

4 recordsLinked to original sources

bioRxiv2025

Mice Mucosal Leishmaniasis model shown high parasite load, increased cytotoxicity and impaired IL-10+ cells response

Mucosal Leishmaniasis is one of the most aggressive clinical manifestations of Leishmania infection disease, characterized by the destruction of nasal and oral tissues. The mechanisms by which this disease occurs are still not well understood due to the lack of effective experimental models. Mucosal leishmaniasis is associated with inflammatory response, especially Th17 response. Based on that, in this work, the immunopathological aspects of the experimental infection of BALB/c mice by Leishmania amazonensis in the mucosa site were evaluated due to high susceptibility and the disease been associated with Th17 response. Three infection modes were performed and compared according to the injection site. Six weeks post infection, mice presented edema in the nasal and premaxillary region, with progressive growth until twelve weeks. The micro-Computerized Tomography and the histology images demonstrated that the parasite inoculation led to destruction of squamous and transitional tissues in NC and NB groups, with several cells harboring amastigotes. Mice infected in the mucosa tissues had higher parasite load and IgG, IgM antibody levels and increased production of cytotoxic mediators such as CD107, granzyme b and perforin, inflammatory cytokines as IFN-{gamma} and IL-17, but lower frequencies of CD4+ IL-10+ cells compared to ear dermis. Taken together, our data shows that L. amazonensis parasites are more proliferative in nasal mucosa and the infection leads to an increased inflammatory response compared to ear dermis, pointing to this model as an interesting approach to understand some features of MCL immunopathology.

immunology↗

bioRxiv2024

IL-17A/IFN-γ producing γ δ T cell functional dichotomy impacts cutaneous leishmaniasis in mice

{gamma}{delta} T cells are innate-like lymphocytes with pleiotropic roles in immune responses to pathogens, often ascribed to their IL-17A-producing or IFN-{gamma}-producing {gamma}{delta} T cell subsets. Here we investigated the impact of this functional dichotomy on cutaneous leishmaniasis, a set of neglected diseases caused by parasites of the Leishmania genus. We demonstrate that in Sv129 mice susceptible to Leishmania amazonensis, V{gamma}4+ {gamma}{delta} T cells are the main source of IL-17A. Furthermore, in type 1 interferon receptor-deficient (A129) mice presenting increased susceptibility to infection, there is a higher frequency of IL-17A-producing {gamma}{delta} T cells when compared to wild-type mice. Mechanistically, we demonstrate that lipophosphoglycan (LPG) of L. amazonensis induces IL-17A-producing {gamma}{delta} T cells. Importantly, C57Bl/6 mice deficient in {gamma}{delta} T cells or in IL-17 receptor (IL-17RA) show reduced lesion sizes, consistent with a pathogenic role of IL-17A-producing {gamma}{delta} T cells in cutaneous leishmaniasis. Conversely, the adoptive transfer of FACS-sorted {gamma}{delta} T cells led to an accumulation of IFN-{gamma}-producing {gamma}{delta} T cells in various susceptible strains of mice which associated with control of lesion development. These data demonstrate a pathophysiological dichotomy in which IL-17A-producing {gamma}{delta} T cells promote pathogenesis, whereas IFN-{gamma}-producing {gamma}{delta} T cells display therapeutic potential in cutaneous leishmaniasis.

immunology↗

bioRxiv2019

Mayaro virus replication restriction and induction of muscular inflammation in mice are dependent on age and type-I interferon response

Mayaro virus (MAYV) is an emergent Arbovirus belonging to the Alphavirus genus from the Togaviridae family which has been circulated in forest regions of American continent through small outbreaks. Recent studies warned for the risk of MAYV dispersion to new areas and for the potential establishment of an urban epidemic cycle. Similar to Chikungunya and other arthritogenic Alphavirus, MAYV-induced disease shows a high prevalence of arthralgia and myalgia that can persist for months. Despite this, knowledge regarding pathogenesis, characteristics of host immune response, and resolution of MAYV infections are still limited. Here we investigated the dependence of age, innate and adaptive immunity for the control of MAYV replication and induction of inflammation in mice. We observed that age and type I interferon response are related to restriction of MAYV infection and tissue inflammation in mice. Moreover, we showed that MAYV continues to replicate persistently in adult recombination activation gene-1 efficient mice (RAG1-/-), indicating that adaptive immunity is essential to MAYV clearance. Despite chronic replication, infected adult RAG1-/- mice did not develop an apparent signal of muscle damage at late infection. On the other hand, MAYV infection induces muscular and paw inflammation in young WT and adult Type I Interferon receptor deficient mice (IFNAR-/-). In addition, MAYV infection triggers an increase in the expression of pro-inflammatory mediators, such as TNF, IL-6, KC, IL-1{beta}, MCP-1, and RANTES, in muscle tissue, and decreases TGF-{beta} expression. Taken together, our study contributes to the comprehension of MAYV pathogenesis, and describes a translational mouse model for further studies of MAYV infection, as well for testing vaccine and therapeutic strategies against this virus.\n\nAuthor SummaryMAYV-induced disease presents a high prevalence of arthralgia and myalgia that potentially persist for months, which is characteristic of the arthritogenic Alphavirus group. However, information regarding MAYV infection and the molecular mechanism of pathogenesis is still scarce. Here we investigated the dependence of age, innate and adaptive immunity for the control of MAYV replication and induction of inflammation in mice. We observed that tissue inflammation and the restriction of MAYV replication in mice are affected by aging and type I interferon response. Besides, we also showed that adaptive immunity was important for MAYV clearance in adult mice. Histological analyses demonstrated that MAYV replication triggered muscular and paw inflammation in young WT and adult type-I interferon receptor deficient mice. In addition, the level of expression of several pro-inflammatory cytokines was increased in the muscle MAYV-infected mice. Our data provide an advance for understanding the molecular mechanism involved in MAYV pathogenesis, as well as describes an in vivo model for further investigations on MAYV infection and for antiviral compounds and vaccine testing.

microbiology↗

bioRxiv2019

Yellow Fever Vaccine Protects Resistant and Susceptible Mice Against Zika Virus Infection

Zika virus (ZIKV) emerged as an important infectious disease agent in Brazil in 2016. Infection usually leads to mild symptoms but severe congenital neurological disorders and Guillain-Barre syndrome have been reported following ZIKV exposure. The development of an effective vaccine against Zika virus is a public health priority, encouraging the preclinical and clinical studies of different vaccine strategies. Here, we describe the protective effect of an already licensed attenuated yellow fever vaccine (17DD) on type-I interferon receptor knockout mice (A129) and immunocompetent (BALB/c) mice infected with ZIKV. Yellow fever virus vaccination results in robust protection against ZIKV, with decreased mortality in the A129 mice, a reduction in the cerebral viral load in all mice, and weight loss prevention in the BALB/c mice. Despite the limitation of yellow fever (17DD) vaccine to elicit antibody production and neutralizing activity against ZIKV, we found that YF immunization prevented the development of neurological impairment induced by intracerebral virus inoculation in adult. Although we used two vaccine doses in our protocol, a single dose was protective, reducing the cerebral viral load. Different Zika virus vaccine models have been tested; however, our work shows that an efficient and certified vaccine, available for use for several decades, effectively protects mice against Zika virus infection. These findings open the possibility for using an available and inexpensive vaccine to a large-scale immunization in the event of a Zika virus outbreak.

immunology↗