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Patkar, R.

Publications and source records attributed to Patkar, R..

5 recordsLinked to original sources

Commensal Escherichia coli colonization triggers Peyer's patch development

The gut microbiota plays a pivotal role in shaping mucosal immunity, yet the specific microbes contributing to lymphoid tissue development remain poorly defined. Here, we identify Escherichia coli, a pioneer commensal bacterium, as a key driver of naive B cell accumulation in gut Peyers patches and lamina propria via a CXCR2-dependent mechanism. We show that E. coli promotes B cell recruitment through the production of curli amyloid fibers, which signal via Toll-like receptor 2 (TLR2). Notably, this effect extends beyond the neonatal period, revealing a broader temporal window for microbial modulation of mucosal immune development. These findings reveal a previously unrecognized role for a defined gut commensal bacterium and its molecular products in orchestrating the formation of gut-associated lymphoid tissue and B cell recruitment.

microbiology↗

Association of secondary metabolite gene clusters with host specialization in the cereal blast fungus Pyricularia oryzae

Fungal plant pathogens constantly evolve and deploy novel peptide and metabolite effectors to break down plant resistance and adapt to new host plants. The blast fungal pathogen Pyricularia oryzae is a single species subdivided into multiple host-specific lineages that have evolved through gain and/or loss of virulence and/or effector related genes through chromosomal rearrangement. Here, we mined 68 genomes of P. oryzae, belonging to six host-specific lineages, to identify secondary metabolite (SM) biosynthetic gene clusters (BGCs) likely associated with potential metabolite effectors involved in host specialization. A similarity network analysis grouped a total of 4501 BGCs into 283 gene cluster families (GCFs), based on the content and architecture of the BGCs. While most of the GCFs were present in all the P. oryzae lineages, two (BGC-O1 and BGC-O2) were found specifically in the Oryza lineage and one (BGC-TLE) was found in the lineage specific to Triticum, Lolium and Eleusine hosts. Further analysis of the phylogenetic relationships between core biosynthetic genes confirmed that BGC-O1, which comprises a reducing polyketide synthase gene (MGG_08236) and four putative tailoring genes, was present only in the Oryza lineage. Importantly, most genes, including MGG_08236, from the BGC-O1 were expressed specifically during pathogenesis. We propose that the Oryza lineage-specific BGC-O1 produces a metabolite effector likely involved in specialization of P. oryzae to the rice host. In addition, we identified five SM genes under positive or balancing selection only in the Oryza lineage, suggesting a role in the interaction with rice specifically. Our findings highlight the importance of further mining novel metabolite effectors in specialization and virulence of the blast fungus to different cereal hosts.

genomics↗

Selective IL-27 production by intestinal regulatory T cells permits gut-specific regulation of Th17 immunity

Regulatory T (Treg) cells are instrumental in establishing immunological tolerance. However, the precise effector mechanisms by which Treg cells control a specific type of immune response in a given tissue remains unresolved. By simultaneously studying Treg cells from different tissue origins under systemic autoimmunity, here we show that IL-27 is specifically produced by intestinal Treg cells to regulate Th17 immunity. Selectively increased intestinal Th17 responses in mice with Treg cell-specific IL-27 ablation led to exacerbated intestinal inflammation and colitis-associated cancer, but also helped protect against enteric bacterial infection. Furthermore, single-cell transcriptomic analysis has identified a CD83+TCF1+ Treg cell subset that is distinct from previously characterized intestinal Treg cell populations as the main IL-27 producers. Collectively, our study uncovers a novel Treg cell suppression mechanism crucial for controlling a specific type of immune response in a particular tissue, and provides further mechanistic insights into tissue-specific Treg cell-mediated immune regulation.

immunology↗

Vacuolar transporter Mnr2 safeguards mitochondrial integrity in aged cells

Aging is associated with altered mitochondrial function. Mitochondrial function is dependent on the magnesium (Mg+2) ion flux. The molecular mechanism underlying Mg+2 homeostasis, especially during aging has not been well understood. We previously demonstrated that the absence of a vacuolar ion transporter Mnr2 accelerates cell death in the older part of the colony in Magnaporthe oryzae presumably due to an altered Mg+2 homeostasis. Localization of Mnr2 as dynamic puncta at the vacuolar membrane especially in the older Magnaporthe cells further suggests its association with aged cells. Interestingly, such vacuolar Mnr2 puncta colocalized with the filamentous mitochondria in the aged cells. Further, we show that aged mnr2{Delta} null cells displayed loss of integrity of mitochondria and vacuoles. Remarkably, exogenously added Mg+2 restored the mitochondrial structure as well as improved the lifespan of mnr2{Delta} null cells. Thus, we uncover a mechanism of maintenance of mitochondrial integrity and function by the ion transporter Mnr2-based Mg+2 homeostasis during aging.

cell biology↗

Dual role for fungal-specific outer kinetochore proteins during cell cycle and development in Magnaporthe oryzae

The outer kinetochore DASH/DAM complex ensures proper spindle structure and chromosome segregation. While DASH complex protein requirement diverges among different yeasts, its role in filamentous fungi has not been investigated so far. We studied the dynamics and role of middle (Mis12) and outer (Dam1 and Ask1) kinetochore proteins in the filamentous fungal pathogen, Magnaporthe oryzae, which undergoes multiple cell cycle linked developmental transitions. Both Dam1 and Ask1, unlike Mis12, were recruited to the nucleus specifically during mitosis. While Dam1 was not required for viability, loss of its function (dam1{Delta} mutant) delayed mitotic progression, resulting in impaired conidial and hyphal development in Magnaporthe. Intriguingly, both Dam1 and Ask1 also localised to the hyphal tips, in the form of punctae oscillating back and forth from the growing ends, suggesting that Magnaporthe DASH complex proteins may play a non-canonical role in polarised growth during interphase, in addition to their function in nuclear segregation during mitosis. Impaired appressorial (infection structure) development and function in the dam1{Delta} mutant suggest that fungus-specific Dam1 complex proteins could be an attractive target for a novel anti-fungal strategy.\n\nSummary StatementDASH complex proteins are differentially recruited to the nucleus during cell division and are intriguingly involved in polarised growth during development and differentiation in the rice blast fungus.

cell biology↗