Biology subjects

Rakib, T.

Publications and source records attributed to Rakib, T..

3 recordsLinked to original sources

bioRxiv2025

CD226 identifies effector CD8+ T cells during tuberculosis and costimulates recognition of Mycobacterium tuberculosis-infected macrophages

CD8+ T cells defend against Mycobacterium tuberculosis (Mtb) infection but variably recognize Mtb-infected macrophages. To define how the diversity of lung parenchymal CD8+ T cells changes during chronic infection, cells from C57BL/6J mice infected for 6- and 41-weeks were analyzed by scRNA-seq. We identified an effector lineage, including a cluster that expresses high levels of cytotoxic effectors and cytokines, and dysfunctional lineage that transcriptionally resembles exhausted T cells. The most significant differentially expressed gene between two distinct CD8+ T cell lineages is CD226. Mtb-infected IFN{gamma}-eYFP reporter mice revealed IFN{gamma} production is enriched in CD226+CD8+ T cells, confirming these as functional T cells in vivo. Purified CD226+ but not CD226- CD8+ T cells recognize Mtb-infected macrophages, and CD226 blockade inhibits IFN{gamma} and granzyme B production. Thus, CD226 costimulation is required for efficient CD8+ T cell recognition of Mtb-infected macrophages, and its expression identifies CD8+ T cells that recognize Mtb-infected macrophages. One Sentence SummaryShinkawa et al. discover that CD226 is a functional marker that distinguishes effector from dysfunctional CD8+ T cells in the Mycobacterium tuberculosis (Mtb)-infected lung and has a crucial role in costimulating CD8+ T cell recognition of Mtb-infected macrophages.

immunology↗

bioRxiv2023

Heterogeneity in lung macrophage control of Mycobacterium tuberculosis is determined by T cells

Following Mycobacterium tuberculosis infection, alveolar macrophages are initially infected but ineffectively restrict bacterial replication. The distribution of M. tuberculosis among different cell types in the lung changes with the onset of T cell immunity when the dominant infected cellular niche shifts from alveolar to monocyte-derived macrophages (MDM). We hypothesize that changes in bacterial distribution among different cell types is driven by differences in T cell recognition of infected cells and their subsequent activation of antimicrobial effector mechanisms. We show that CD4 and CD8 T cells efficiently eliminate M. tuberculosis infection in alveolar macrophages, but they have less impact on suppressing infection in MDM, which may be a bacterial niche. Importantly, CD4 T cell responses enhance MDM recruitment to the lung. Thus, the outcome of infection depends on the interaction between the T cell subset and the infected cell; both contribute to the resolution and persistence of the infection.

immunology↗

bioRxiv2018

Microbiota-independent antiviral protection conferred by aminoglycoside antibiotics

Antibiotics are widely used to treat infections in humans. However, the impact of antibiotic use on host cells is understudied. We have identified a novel antiviral effect of commonly used aminoglycoside antibiotics. We show that mucosal application of aminoglycosides increased host resistance to a broad range of viral infections including herpes simplex viruses, influenza A virus and Zika virus. Aminoglycoside treatment also reduced viral replication in primary human cells. This antiviral activity was independent of the microbiota as aminoglycoside treatment protected germ-free mice. Microarray analysis uncovered a marked upregulation of transcripts for interferon-stimulated genes (ISGs) following aminoglycoside application. ISG induction was mediated by TLR3, and required TIR-domain-containing adapter-inducing interferon-{beta} (TRIF), signaling adaptor, and interferon regulatory factors 3 (IRF3) and IRF7, transcription factors that promote ISG expression. XCR1+ dendritic cells, which uniquely express TLR3, were recruited to the vaginal mucosa upon aminoglycoside treatment and were required for ISG induction. These results highlight an unexpected ability of aminoglycoside antibiotics to confer broad antiviral resistance in vivo.

immunology↗