Biology subjects

Argilaguet, J.

Publications and source records attributed to Argilaguet, J..

4 recordsLinked to original sources

bioRxiv2025

Distinct cytotoxic cell subsets underlie protective and non-protective immunity to African swine fever virus

Limited understanding of African swine fever (ASF) immunity remains a major barrier to the rational development of safe and effective vaccines. While antibody-mediated protection is still poorly defined, growing evidence highlights a central role for cellular immunity. In particular, cytotoxic cells have emerged as key components to control ASF virus (ASFV) infection. However, the contribution of individual cytotoxic subsets across different virological and immunological contexts is not well characterised. Here, we investigated cytotoxic responses during BA71{Delta}CD2 live attenuated vaccine (LAV)-induced protection and during late-stage lethal ASFV infection, and demonstrated the involvement of different cytotoxic subsets in each scenario. Early increases in perforin-producing CD8{beta}+ T cells in blood after immunisation coincided with the onset of protection. At later time points, elevated levels of these cells after in vitro ASFV-specific stimulation correlated with survival to lethal challenge, supporting their central role in protective immunity. Additional correlates of protection during recall responses included CD4+CD8{beta}+ cytotoxic T cells, IFN{gamma}-producing cells, and ASFV-specific antibodies, illustrating the multifactorial nature of immunity to ASF. In contrast, pigs with acute ASF exhibited a distinct cytotoxic profile characterised by broad increases across multiple perforin-producing subsets. Although all of them showed reduced susceptibility to ASFV-induced lymphopenia, only perforin-producing NK and{gamma}{delta} T cells correlated with viremia, suggesting their active involvement during late disease. Together, these findings advance our understanding of cytotoxic responses to ASFV and identify cytotoxic T cells, alongside other immune components, as potential correlates of protection that may guide future vaccine development.

immunology↗

bioRxiv2024

Comparative impact of porcine reproductive and respiratory virus and swine influenza A virus infections on respiratory lymph nodes B cells and macrophages.

Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) strongly impacts the pig rearing sector due to its persistence in infected animals. Interestingly, although the PRRSV family exhibits considerable genome variability, with the PRRSV-1 and PRRSV-2 subtypes having been finally classified in two different species (Betaarterivirus suid 1 and 2). Both viruses, as well as their derived-attenuated vaccine strains, persist for months, due in part to their ability to delay the appearance of neutralizing antibodies. Thanks to extensive efforts over the past years, we have developed the capability to perform in-depth analysis of the previously poorly understood porcine inverted lymph node (LN). In this study, by comparing the early stages of LN B cell maturation upon PRRSV-1 infection to those induced upon the acute swine influenza A virus infection, we highlighted PRRSV-specific mechanisms, including the expression of PD-L1 in efferent macrophages, the induction of extrafollicular plasmocytes, and the influx of inflammatory monocytes/macrophages. Studies on PRRSV-2 infections report observations compatible with our results, that thus might be generalized to all PRRSV-strains. Moreover, these mechanisms can be compared with those used by the human immunodeficiency virus (HIV) and the murine chronic lymphocytic choriomeningitis virus (LCMV) to hijack the immune response. These similarities can be harnessed to develop new strategies to improve the development of more efficient anti-PRRSV vaccines.

immunology↗

bioRxiv2022

Schlafen 12 restricts HIV-1 latency reversal by a codon-usage dependent post-transcriptional block in CD4+ T cells

Latency is a major barrier towards virus elimination in HIV-1-infected individuals. Yet, the mechanisms that contribute to the maintenance of HIV-1 latency are incompletely understood. Here we describe the Schlafen 12 protein (SLFN12) as an HIV-1 restriction factor that establishes a post-transcriptional block in HIV-1-infected cells and thereby inhibits HIV-1 replication and virus reactivation from latently infected cells. The inhibitory activity is dependent on the HIV-1 codon usage and on the SLFN12 RNase active sites. Within HIV-1- infected individuals, SLFN12 expression in PBMCs correlated with HIV-1 plasma viral loads and proviral loads suggesting a link with the general activation of the immune system. Using an RNA FISH-Flow HIV-1 reactivation assay, we demonstrate that SLFN12 expression is enriched in infected cells positive for HIV-1 transcripts but negative for HIV-1 proteins. Thus, codon-usage dependent translation inhibition of HIV-1 proteins participates in HIV-1 latency and can restrict the amount of virus release after latency reversal.

immunology↗

bioRxiv2018

Time-resolved systems analysis reveals a critical role of XCR1+ 1 dendritic cells in the maintenance of effector T cells during chronic viral infection

Upon a viral infection, the host immune system attempts to eradicate the virus. However, once the infection threat seems overwhelming, the infected host actively shuts down effector responses to reduce immunopathology. The price to pay for this is the establishment of a chronic infection that is only partially controlled by a lower level immune response. The genetic networks underlying this infection fate decision and the immune adaptation to the lower level response are not well understood. Here we used an integrated approach of gene coexpression network analysis of time-resolved splenic transcriptomes and immunological analysis to characterize the host response to acute and chronic lymphocytic choriomeningitis virus (LCMV) infections. We found first, an early attenuation of inflammatory monocyte/macrophage prior to the onset of T cell exhaustion and second, a critical role of the XCL1-XCR1 communication axis during the functional adaptation of the T cell response to the chronic infection state. These findings not only reveal an important feedback mechanism that couples T cell exhaustion with the maintenance of a lower level of effector T cell response but also suggest therapy options to better control virus levels during the chronic infection phase.\n\nAuthor SummaryThe outcomes of viral infections are the result of dynamic interplays between infecting viruses and induced host responses. They can be categorized as either acute or chronic depending on temporal virus-host relationships. Chronic infections are associated with immune exhaustion, a partial shut-down of effector responses. The processes underlying infection fate decisions are incompletely understood. Here we analyzed, on a systems level, infection-fate-specific gene signatures and the resulting adaptive processes of the host. We used the well-established lymphocytic choriomeningitis virus infection mouse model which has been instrumental to detect many fundamental processes in the virus-immune system crosstalk that are also relevant in human infections. We show an early attenuation of macrophage-mediated inflammation and an involvement of cross-presenting dendritic cells in the maintenance of an antiviral cytotoxic T cell response and virus control in the chronic infection phase. Together our data demonstrate a delicate adaptation process towards a chronic virus infection with both immunosuppressive and immunostimulatory processes. We fill a knowledge gap regarding the mechanisms of effector T cell maintenance and provide a new rational for targeted therapeutic vaccination.

immunology↗