Biology subjects

Uppalapati, C. K.

Publications and source records attributed to Uppalapati, C. K..

2 recordsLinked to original sources

bioRxiv2024

Influenza A Virus Disruption of Dendritic Cell-Natural Killer Cell Crosstalk Impacts Activation of Helper and Cytotoxic T cell Subsets

Dendritic cells (DC) and Natural killer (NK) cells engage in reciprocal interactions to trigger an efficient innate immune response while governing the adaptive immune response. Here we used an ex vivo autologous human primary immune cell co-culture of DCs and NK cells to investigate the impact of DC-NK cell crosstalk on activation of CD4+ and CD8+ naive T cell responses to influenza A viral (IAV) infection. Using multiparameter flow cytometry, we observed that culturing T cells with DC and NK cells led to enhanced expression of CD69 and CD25 activation markers and increased proliferative ability of both CD4+ and CD8+ T cell subsets. Exposure of DCs to the pandemic A/California/07/2009 (H1N1) strain in NK cell co-culture led to a reduced frequency of CD4+CD69+, CD8+CD69+, CD4+CD25+, CD8+CD25+ T cell subsets and a reduced expansion of CD4+ T cells. The IAV-mediated curtailment of T cell activation was dependent on the ability of A/California/07/2009 (H1N1) to replicate as inactivation of the virus rescued expression of CD69, CD25 on both CD4+ and CD8+ T cell subsets and triggered expansion of CD4+ T cells. Further, we discovered exposure of DCs to the A/Victoria/361/2011 (H3N2) IAV strain also significantly impaired expression of CD69 on CD4+ and CD8+ T cells and CD25 on CD8+ T cells. In contrast with the A/California/07/2009 (H1N1 strain), inactivation of A/Victoria/361/2011 (H3N2) failed to fully restore T cell expression of CD69 and CD25 and proliferation. Collectively, these data demonstrate that IAV partially usurps the ability of DC-NK cell crosstalk to activate naive CD4+ and CD8+ T cells in a strain-dependent manner. These data may inform the immunological signals required to trigger a potent cellular immune response to IAV, which may elicit broader and more durable protection than current inactivated vaccine platforms.

immunology↗

bioRxiv2022

Dendritic cell-Natural Killer cell Crosstalk Modulates T cell activation in Response to Influenza A Viral Infection

Influenza viruses lead to substantial morbidity and mortality including ~3-5 million cases of severe illness and ~290,000-650,000 deaths annually. One of the major hurdles regarding influenza vaccine efficacy is generating a durable, robust cellular immune response. Appropriate stimulation of the innate immune system is key to generating cellular immunity. Crosstalk between innate dendritic cells (DC) and natural killer (NK) cells plays a key role in activating virus-specific T cells, yet the mechanisms used by influenza A viruses (IAV) to govern this process remain incompletely understood. Here, we used an ex vivo autologous human primary immune cell culture system to evaluate the impact of genetically distinct IAV strains on DC-NK cell crosstalk and subsequent T cell activation. We report that the addition of NK cells to cultures containing both DCs and naive T cells led to an increase in the frequency of CD69+ and CD25+ T cells and elevated levels of IFN-{gamma}, TNF, and IL-10. However, upon IAV infection of DCs, the addition of NK cells to cultures no longer increased the frequency of CD25+ T cells nor elevated IFN-{gamma}, TNF, and IL-10 cytokine levels. Investigation of the impact of IAV infection on DC-NK crosstalk revealed that exposure of DCs to influenza virus in co-culture led to an increased frequency of HLA-DR+ and a decreased frequency of CD83+ and CD86+ cells-molecules involved in stimulating T cell activation. An expansion of an HLA-DR+ NK cell subset was observed following culture with influenza-infected DCs in a contact-dependent and cytokine independent-manner. Overall, our results indicate a role for DC-NK cell crosstalk in T cell priming in the context of influenza infection, informing the immunological mechanisms that could be manipulated for the next generation influenza vaccine or immunotherapeutic.

immunology↗