Biology subjects

Kumar, P. N.

Publications and source records attributed to Kumar, P. N..

3 recordsLinked to original sources

bioRxiv2025

Angiogenic CD8 T cells from PWH induce Granzymes-dependent PAR1 activation promoting endothelial inflammation

In people with HIV (PWH), T cell immune activation and endothelial inflammation are contributors of the increased cardiovascular risk, however the mechanisms remain poorly understood. PAR1 connects the coagulation cascade, endothelial cells and CD8 T cells at the site of endothelial inflammation and we hypothesized that HIV driven CD8 T cell immune activation alters endothelial repair mechanisms. Endothelial repair is partially mediated by angiogenic T (Tang) cells that facilitate proliferation of endothelial cells, and differentiation of endothelial progenitor cells at site of vascular injury. During LCMV infection, we identified a subset of CD31highCD8 T cells that exhibited a long-lived memory precursor phenotype (CD127+KLRG1-) and secreted the proangiogenic cytokine vascular endothelial growth factor (VEGF) after viral control. Furthermore, in PWH, the frequencies of CD8 Tang cells were reduced and showed an activated phenotype and expression of granzymes. GZMA+GZMB+CD8 Tang cells correlated with atherosclerotic cardiovascular disease (ASCVD) risk. In vitro, granzyme dependent PAR1 activation led to calcium mobilization and secretion of proinflammatory cytokines IL-6, IL-8 and angiopoietin-2 by primary human endothelial cells. Altogether, these findings suggest that CD8 T cells are involved in immunity against viruses and endothelial homeostasis and HIV driven immune activation alters these functions.

immunology↗

bioRxiv2024

Grey Pineapple Mealybug, Dysmicoccus neobrevipes Beardsley: A New Devastating Pest of Tuberose in India

Tuberose (Agave amica) is a highly valued flower crop in India, known for its consistently high returns and ability to thrive in various climatic conditions. Severe outbreaks of the grey pineapple mealybug, Dysmicoccus neobrevipes Beardsley (Hemiptera: Pseudococcidae), have been observed in several villages of the Pune district, Maharashtra (India), since 2021, leading to significant economic losses. This report provides an illustrative morphological diagnosis of D. neobrevipes and basic information on its field establishment, impact on tuberose crops, nature of the damage and field symptoms etc. Surveys conducted in major tuberose-growing areas of Pune district (Maharashtra) revealed that the mealybug primarily infests the underground and basal portion of tuberose plants, causing stunted growth, drooping, and ultimately death of the plants. D. neobrevipes produces honeydew, fostering sooty mold growth that impairs photosynthesis, reduces flower yield. It also infests tuberose bulbs, spoiling them in storage. Based on primary scientific literature, this study represents the first scientifically confirmed record of D. neobrevipes as a new pest of tuberose in India. The ant species Solenopsis geminata was found attending to mealybug colonies, aiding their spread and creating a nuisance for farmers during routine field activities. A total of 87.09% of the surveyed fields (n=62) showed mealybug infestation, ranging from 68% to 97%. Raising awareness among the farmers and implementing regular monitoring in tuberose-growing areas are crucial steps for developing effective management practices and preventing the further spread of this pest to other regions.

zoology↗

bioRxiv2023

Neutrophil-derived IL-17 limits protective host responses and promotes tuberculosis pathogenesis

The protective correlates of Mycobacterium tuberculosis (Mtb) infection-elicited host immune responses are incompletely understood. Here, we report pro-pathogenic crosstalk involving Ly6G+granulocytes (Ly6G+Gra), IL-17 and COX2. We show that in the lungs of Mtb-infected wildtype mice, either BCG-vaccinated or not, most intracellular bacilli are Ly6G+Gra-resident four weeks post-infection onwards. In the genetically susceptible IFN{psi} -/- mice, excessive Ly6G+Gra infiltration correlates with severe bacteraemia. Neutralizing IL-17 (anti-IL17mAb) and COX2 inhibition by celecoxib reverse Ly6G+Gra infiltration, associated pathology and death in IFN{psi} -/- mice. Surprisingly, Ly6G+Gra also serves as the major source of IL-17 in the lungs of Mtb-infected WT or IFN{psi} -/- mice. The IL-17-COX2-Ly6G+Gra interplay also operates in WT mice. Inhibiting ROR{psi}t, the key transcription factor for IL-17 production or COX2, reduces the bacterial burden in Ly6G+Gra, leading to reduced bacterial burden and pathology in the lungs of WT mice. In the Mtb-infected WT mice, COX2 inhibition abrogates IL-17 levels in the lung homogenates and significantly enhances BCGs protective efficacy, mainly by targeting the Ly6G+Gra-resident Mtb pool, a phenotype also observed when IL-17 is blocked by ROR{psi}t inhibitor. Furthermore, in pulmonary TB patients, high neutrophil count and IL-17 correlated with adverse treatment outcomes. Together, our results suggest that IL-17 and PGE2 are the negative correlates of protection, and we propose targeting the pro-pathogenic IL-17-COX2-Ly6G+Gra axis for TB prevention and therapy.

immunology↗