Biology subjects

Boccardo, S.

Publications and source records attributed to Boccardo, S..

5 recordsLinked to original sources

bioRxiv2026

Dual Th1 and tissue-repair Treg cells accumulate in skeletal muscle preserving tissue integrity during infection

Chronic infections require mechanisms that limit tissue damage while preserving pathogen control, yet the contribution of regulatory T (Treg) cells to this balance remains unclear. In this study, we characterized Treg cell responses during a chronic parasitic infection using experimental Trypanosoma cruzi infection as a model of persistent low-level parasitism and chronic tissue inflammation. We found that, although Treg cell numbers decline in the spleen, they accumulate in parasite-affected tissues such as skeletal muscle, where they adopt a combined Th1-associated and tissue-repair program. Systemic Treg cell depletion had limited impact on immune and disease-associated parameters, whereas local depletion in skeletal muscle exacerbated tissue damage and increased parasite burden. Moreover, transient systemic perturbation of Treg cells during the acute phase impaired their long-term accumulation in skeletal muscle, resulting in increased tissue damage and parasite burden during chronic infection. Additionally, accumulation of reparative Treg cells in skeletal muscle was impaired in the absence of ST2. Together, these findings identify a tissue-adapted Treg cell population that integrates inflammatory and reparative programs to preserve skeletal muscle integrity during chronic parasitic infection. SUMMARYChronic parasite infection drives the emergence of tissue-adapted regulatory T cells that integrate Th1-associated and tissue-repair programs. These cells accumulate in skeletal muscle, where they preserve tissue integrity while contributing to microbial control, highlighting the dynamic specialization of Treg cells across disease stages.

immunology↗

bioRxiv2024

Tissue damage during acute Trypanosoma cruzi infection is associated with reduced reparative regulatory T cell response and can be attenuated by early interleukin-33 administration.

Tissue-repair regulatory T cells (trTregs) constitute a specialized regulatory subset renowned for orchestrating tissue homeostasis and repair. While extensively investigated in sterile injury models, their role in infection-induced tissue damage and the regulation of protective antimicrobial immunity remains largely unexplored. This investigation examines trTregs dynamics during acute Trypanosoma cruzi infection, a unique scenario combining extensive tissue damage with robust antiparasitic CD8+ immunity. Contrary to conventional models of sterile injury, our findings reveal a pronounced reduction of trTregs in secondary lymphoid organs and tissues during acute T. cruzi infection. This unexpected decline correlates with systemic as well local tissue damage, as evidenced by histological alterations and downregulation of repair-associated genes in skeletal muscle. Remarkably, a parallel decrease in systemic levels of IL-33, a crucial factor for trTregs survival and expansion, was detected. We found that early treatment with systemic recombinant IL-33 during infection induces a notable surge in trTregs, accompanied by an expansion of type 2 innate lymphoid cells and parasite-specific CD8+ cells. This intervention results in a mitigated tissue damage profile and reduced parasite burden in infected mice. These findings shed light on trTregs biology during infection-induced injury and demonstrate the feasibility of enhancing a specialized Tregs response without impairing the magnitude of effector immune mechanisms, ultimately benefiting the host. Furthermore, this study settles groundwork of relevance for potential therapeutic strategies in Chagas disease and other infections. AUTHOR SUMMARYChagas disease, caused by the protozoan Trypanosoma cruzi, induces severe organ damage caused by the interplay between the parasite and the immune response. In our investigation, we delved into the role of tissue-repair regulatory T cells (trTregs) during the acute phase of T. cruzi infection in mice. Surprisingly, we observed a reduction in trTregs during the peak of tissue damage, contrary to their usual accumulation after injury in other contexts. This decline aligned with decreased levels of interleukin-33, a critical factor for trTregs survival. Administering interleukin-33 at early infection times not only boosted trTregs but also expanded other reparative and antiparasitic immune cells. Consequently, these treated mice exhibited reduced damage and lower parasite levels in tissues. Our findings offer insights into trTregs behavior during infection-induced injury, suggesting a promising avenue for therapeutic interventions in Chagas disease and related conditions. This study lays the groundwork for potential strategies that balance the immune response, supporting tissue repair without compromising the ability to control the infection, which could have broader implications for infectious diseases and tissue damage-related pathologies.

immunology↗

bioRxiv2023

CD39 expression by regulatory T cells drives CD8+ T cell suppression during experimental Trypanosoma cruzi infection

An imbalance between suppressor and effector immune responses may preclude cure in chronic parasitic diseases. In the case of Trypanosoma cruzi infection, specialized regulatory Foxp3+ T (Treg) cells suppress protective type-1 effector responses. Herein, we investigated the kinetics and underlying mechanisms behind the regulation of protective parasite-specific CD8+ T cell immunity during acute T. cruzi infection. Using the DEREG mouse model, we found that Treg cells play a critical role during the initial stages after T. cruzi infection, subsequently influencing CD8+ T cells. Early Treg cell depletion increased the frequencies of polyfunctional short-lived, effector T cell subsets, without affecting memory precursor cell formation or the expression of activation markers. In addition, Treg cell depletion during early infection minimally affected the antigen-presenting cell response but it boosted CD4+ T cell responses before the development of anti-parasite effector CD8+ T cell responses. Crucially, the absence of CD39 expression on Treg cells significantly bolstered effector parasite-specific CD8+ T cell responses, leading to improved parasite control during T. cruzi infection. Our work underscores the crucial role of Treg cells in regulating protective anti-parasite immunity and provides evidence that CD39 expression by Treg cells represents a key immunomodulatory mechanism in this infection model.

immunology↗

bioRxiv2022

Interleukin-17 signaling influences CD8+ T cell immunity and tumor progression according to the IL-17 receptor subunit expression pattern in cancer cells

The role of IL-17 mediated immune responses in cancer is conflicting as pre-clinical and clinical results show tumor-promoting as wel as tumor-repressing functions. Herein, we used syngeneic tumor models from different tissue origins as a tool to evaluate the role of IL-17 signaling in cancer progression, dissecting the effects in cancer cell growth and tumor immunity. We show that absence of IL-17RA or IL-17A/F expression in the host has contrasting effects in the in vivo growth of different tumor types. We observed that lack of IL-17A/F-IL-17RA signaling in host cells changed the expression pattern of several mediators within the tumor microenvironment in a cancer-type specific manner. Deficiencies in host IL-17RA or IL-17A/F expression resulted in reduced antitumor CD8+ T cell immunity in all cancer models and in tumor-specific changes in several lymphoid cell populations. These findings were associated to particular patterns of expression of cytokines (IL-17A and IL-17F) and receptor subunits (IL-17RA, IL-17RC and IL-17RD) of the IL-17 family in the injected tumor cell lines that, in turn, dictated tumor cell responsiveness to IL-17. We identified IL-17RC as an important determinant of the IL-17-mediated transcriptional response in tumor cells and; consequently, as a predictive biomarker of the overall effect of IL-17 signaling in tumor progression. Our findings contribute to unraveling the molecular mechanisms underlying the divergent activities of IL-17 in cancer and provide rational targets for immunotherapies based on personalized approaches.

immunology↗

bioRxiv2019

Manganese-enhanced MRI (MEMRI) in breast and prostate cancers: exploring the potential role of calcium receptors.

ProceduresTo assess the relationship between Manganese Enhanced Magnetic Resonance Imaging (MEMRI) and the expression of calcium receptors in human prostate and breast cancer animal models.\n\nMethodsNOD/SCID mice were inoculated with MDA-MB-231 breast cancer cells and prostate PC3 cancer cells to develop orthotopic or pseudometastatic cancer animal models. Mice were studied on a clinical 3T scanner by using a prototype birdcage coil before and after intravenous injection of MnCl2. Assessment of receptors status was carried out after the MR images acquisition by immunohistochemistry on excised tumours.\n\nResultsManganese contrast enhancement in breast or prostate cancer animal models well correlated with CaSR expression (p<0.01), whereas TRPV6 expression levels appeared not relevant to the Mn uptake.\n\nConclusionMEMRI appears an efficient tool to characterize human breast and prostate cancer animal models in the presence of different expression level of CaSR.

cancer biology↗