Biology subjects

Gazzoni, Y.

Publications and source records attributed to Gazzoni, Y..

4 recordsLinked to original sources

bioRxiv2026

Distinct profiles and antibody production by splenic and lymph node antibody-secreting cells in Trypanosoma cruzi infection

Evidence from bone marrow and intestinal lamina propria studies indicates that antibody-secreting cell (ASC) characteristics are shaped by the local microenvironment; yet whether secondary lymphoid organs harbor distinct ASC populations during infection remains unclear. Here, we investigated plasmablasts (PB) from the spleen and inguinal lymph nodes (LN) in acute Trypanosoma cruzi infection. Although PB from both tissues expressed canonical ASC markers, they displayed distinct transcriptional, phenotypic, and functional profiles. Splenic PB upregulated genes and proteins associated with inflammation, immunomodulation, and B-cell interactions. Activated and naive B cells also exhibited tissue-specific transcriptional programs, suggesting that local cues influence B-cell differentiation. Consistent with these differences, spleens from infected mice contained more T follicular helper cells, whereas LN were enriched in regulatory T cells. High-dimensional flow cytometry identified multiple PB subsets differentially represented between tissues. Functionally, splenic PB secreted higher levels of IgM, IgA, and IgG, including both parasite-specific and autoreactive antibodies. In contrast, LN PB preferentially produced IgG against peptide 72 of the shed acute-phase antigen (SAPA), despite lower overall T. cruzi-specific antibody production. These findings demonstrate that secondary lymphoid organs harbor distinct PB populations adapted to their local microenvironments during acute infection

immunology↗

bioRxiv2026

Tissue-distinct Features of Follicular Cytotoxic CD8+ T Cells in Trypanosoma cruzi infection

T follicular cytotoxic (Tfc) cells are a specialized subset of CD8 T lymphocytes that combine helper and cytotoxic functions. While their phenotypic and functional properties have been described in several infectious and inflammatory settings, little is known whether Tfc cells exhibit distinct characteristics across secondary lymphoid organs. Using acute Trypanosoma cruzi infection as a model of systemic immune activation, we performed a comparative phenotypic, transcriptomic, metabolic, and functional characterization of Tfc cells arising in the spleen and inguinal lymph nodes. Tfc cells emerged transiently in both organs with similar kinetics and antigen specificity yet segregated primarily according to tissue of analysis at the transcriptional level. Splenic Tfc cells exhibited enhanced glycolytic and mTORC1-associated signatures, increased mitochondrial mass, and stronger cytotoxic and B cell helper functions, promoting immunoglobulin production and plasmablast death. In contrast, Tfc cells from lymph node preferentially displayed memory-associated features, including higher CD127 and CD122 expression, increased IL-2 production, and preferential persistence during chronic infection. Together, these findings demonstrate that Tfc cells are not a homogeneous population but can adopt organ-associated transcriptional, metabolic, and functional states during T. cruzi infection.

immunology↗

bioRxiv2026

A mouse model to study Rio Negro virus pathogenesis: a neglected member of the Venezuelan equine encephalitis virus complex

Rio Negro virus (RNV) is an enzootic alphavirus and a member of the Venezuelan equine encephalitis virus (VEEV) complex. Despite its wide circulation in South America, RNV remains a neglected pathogen with no established wild-type animal model to study its pathogenesis. In this study, we developed a lethal mouse model using 18-day-old wild-type C57BL/6 mice to characterize the systemic and neurological features of RNV infection. Following subcutaneous inoculation, RNV exhibited rapid systemic dissemination with a brief and low-titer viremic phase and high viral loads in lymphoid tissues, pancreas, brains, and lungs. Notably, infected mice developed progressive neurological signs, including ataxia and hindlimb paralysis, culminating in 100% lethality. Histopathological analysis revealed significant damage, highlighted by a striking collapse of the splenic architecture, inflammatory and remodeling changes in the lungs, and prominent inflammatory infiltrates with neurodegenerative changes in the brain. The splenic disruption was further evaluated by immunofluorescence analysis of the spleen, which showed a consistent loss of compartmentalization, characterized by an atypical infiltration of CD8+ T cells into B-cell follicles. The terminal stage of disease was characterized by extensive neuroinflammation and neurodegeneration. Histological examination of the brain revealed meningoencephalitis, robust astrogliosis, and widespread somatodendritic and terminal degeneration, particularly clustered around blood vessels. These findings were supported by cytokine analysis of brain homogenates, which showed a significant upregulation of IFN-{gamma}, IL-6, and MCP-1/CCL2 during symptomatic stages. Collectively, these findings establish a reproducible, non-genetically modified animal model that reveals the pathogenic potential of RNV in the context of immune immaturity characteristic of early life. By identifying these specific pathological and neuroinflammatory markers, our study provides a foundational experimental framework to investigate the mechanisms underlying RNV emergence and host-pathogen interactions within the VEEV complex. Author summaryMany viruses circulate silently in nature, hidden within animal populations, until environmental or social changes bring them into contact with humans. The Rio Negro virus is one such example. Despite being closely related to the better-known Venezuelan equine encephalitis virus and showing evidence of circulation in South America, RNV has remained largely overlooked by the scientific community and public health authorities. In this study, we established a new experimental model using infant mice that allowed us to observe how the virus spreads and causes damage. We found that the virus rapidly reaches the brain and other vital organs, causing severe inflammation in the brain, inflammatory changes in the lungs, and a breakdown of the immune systems organization in the spleen. By using a genetically unmodified model, we were able to observe the infection in a host with an intact but naturally immature immune system. This approach avoids the artificial conditions of genetic engineering while providing a more realistic window into how host age and developmental stages can influence the outcome of neglected viral infections. We believe our work is a first step toward understanding how this overlooked virus emerges and highlights the need to monitor and prepare for "silent" pathogens that could pose a risk to public health in an era of intensifying human activity and ecological pressure.

pathology↗

bioRxiv2019

CD8+ T cell immunity is compromised by anti-CD20 treatment and rescued by IL-17A

Treatment with anti-CD20, used in many diseases in which B cells play a pathogenic role, has been associated with susceptibility to intracellular infections. Here, we studied the effect of anti-CD20 injection on CD8+ T cell immunity using an experimental model of Trypanosoma cruzi infection, in which CD8+ T cells play a pivotal role. C57BL/6 mice were treated with anti-CD20 for B cell depletion prior to T. cruzi infection. Infected anti-CD20-treated mice exhibited a CD8+ T cell response with a conserved expansion phase followed by an early contraction, resulting in a strong reduction in total and parasite-specific CD8+ T cells at 20 days postinfection. Anti-CD20 injection decreased the number of effector and memory CD8+ T cells and reduced the frequency of proliferating and cytokine producing CD8+ T cells. Accordingly, infected anti-CD20-treated mice presented a lower cytotoxicity of T. cruzi peptide-pulsed target cells in vivo. All of these alterations in CD8+ T cell immunity were associated with increased tissue parasitism. Anti-CD20 injection also dampened an established CD8+ T cell response, indicating that B cells were involved in the maintenance rather than the induction of CD8+ T cell immunity. Anti-CD20 injection also resulted in a marked reduction in the frequency of IL-6- and IL-17A-producing cells, and only rIL-17A injection partially restored the CD8+ T cell response in infected anti-CD20-treated mice. Thus, anti-CD20 reduced CD8+ T cell immunity, and IL-17A is a candidate for rescuing deficient responses either directly or indirectly.\n\nImportanceMonoclonal antibody targeting the CD20 antigen on B cells is used to treat the majority of Non-Hodgkin lymphoma patients and some autoimmune disorders. This therapy generates adverse effects, notably opportunistic infections and activation of viruses from latency. Here, using the infection murine model with the intracellular parasite Trypanosoma cruzi, we report that anti-CD20 treatment not only affects B cell response but also CD8+ T cells, the most important immune effectors involved in control of intracellular pathogens. Anti-CD20 treatment, directly or indirectly, affects cytotoxic T cell number and function and this deficient response was rescued by the cytokine IL-17A. The identification of IL-17A as the cytokine capable of reversing the poor response of CD8+ T cells provide information about a potential therapeutic treatment aimed at enhancing defective immunity induced by B cell depletion.

immunology↗