Immuno-microbial crosstalk in aplastic anemia: Role of gut and viral triggers

Aplastic anemia (AA) is a rare but life-threatening hematological disorder, manifested in bone marrow failure and pancytopenia, which occurs worldwide due to the preferential immune mediated destruction of hematopoietic stem and progenitor cells. Despite the autoimmune etiology of AA, recent findings emphasize the key role of microbial and viral factors in the pathogenesis of AA by driving the host immune dysregulation. We delve into the immune-microbial crosstalk that is relevant in AA pathogenesis to provide novel insights related to gut microbial ecology, microbial metabolites, viral infections mediated inflammation and cytotoxicity against bone marrow components. Additionally, providing the roadmap of current knowledge for immune-mediated bone marrow failure focusing on activated cytotoxic T cells, altered regulatory T cells and proinflammatory cytokines. Imbalanced immune activation via defects in gut barrier function which promotes pathogen-associated molecular patterns (PAMPs) signaling through Toll-like receptors (TLRs) and other innate sensors. Considering the role of viral trigger such as Parvovirus B19, Epstein-Barr and Hepatitis as inducers of dysregulated immunity and their ability to affect antigen presentation, T cell receptor repertoires, and interferon pathways. We also delineate the potential of targeting the gut-immune axis for personalized AA therapy, including potential microbiome-directed interventions, antiviral and anti-cytokine approaches, as promising complement lines for standard immunosuppression therapy in AA. This cited approach will provide the advanced and novel clinical paradigm for the interconnected immune-microbial signals in pathogenesis of AA which promotes the host immune surveillance and also lead to precision medicine in AA treatment.