Transgenic mouse models support a protective role of type I IFN response in SARS-CoV-2 infection-related lung immunopathology and neuroinvasion.

Type I interferon (IFN-I) response is the first line of host defense against invading viruses. In the absence of definite mouse models, the role of IFN-I in SARS-CoV-2 infection remains perplexing. Here, we develop two mouse models, one with constitutively high IFN-I response (hACE2; Irgm1) and the other with dampened IFN-I response (hACE2; Ifnar1), to comprehend the role of IFN-I response.

Selective autophagy of RIPosomes maintains innate immune homeostasis during bacterial infection.

The NOD1/2-RIPK2 is a key cytosolic signaling complex that activates NF-κB pro-inflammatory response against invading pathogens. However, uncontrolled NF-κB signaling can cause tissue damage leading to chronic diseases. The mechanisms by which the NODs-RIPK2-NF-κB innate immune axis is activated and resolved remain poorly understood.

Innate immunity and inflammophagy: balancing the defence and immune homeostasis.

Extensive crosstalk exists between autophagy and innate immune signalling pathways. The stimuli that induce pattern recognition receptor (PRR)-mediated innate immune signalling pathways, also upregulate autophagy. The purpose of this increased autophagy is to eliminate the stimuli and/or suppress the inflammatory pathways by targeted degradation of PRRs or intermediary proteins (termed 'inflammophagy').

Inhibition of IRGM establishes a robust antiviral immune state to restrict pathogenic viruses.

The type I interferon (IFN) response is the major host arsenal against invading viruses. IRGM is a negative regulator of IFN responses under basal conditions. However, the role of human IRGM during viral infection has remained unclear.

Unravelling the potential of gut microbiota in sustaining brain health and their current prospective towards development of neurotherapeutics.

Increasing incidences of neurological disorders, such as Parkinson's disease (PD), multiple sclerosis (MS), Alzheimer's disease (AD) and amyotrophic lateral sclerosis (ALS) are being reported, but an insight into their pathology remains elusive. Findings have suggested that gut microbiota play a major role in regulating brain functions through the gut-brain axis. A unique bidirectional communication between gut microbiota and maintenance of brain health could play a pivotal role in regulating incidences of neurodegenerative diseases.

IRGM links autoimmunity to autophagy.

IRGM is a genetic risk factor for several autoimmune diseases. However, the mechanism of IRGM-mediated protection in autoimmunity remains undetermined. The abnormal activation of type I interferon (IFN) response is one of the significant factors in the pathogenesis of several autoimmune diseases.

Autoimmunity gene IRGM suppresses cGAS-STING and RIG-I-MAVS signaling to control interferon response.

Activation of the type 1 interferon response is extensively connected to the pathogenesis of autoimmune diseases. Loss of function of Immunity Related GTPase M (IRGM) has also been associated to several autoimmune diseases, but its mechanism of action is unknown. Here, we found that IRGM is a master negative regulator of the interferon response.

TRIM16 employs NRF2, ubiquitin system and aggrephagy for safe disposal of stress-induced misfolded proteins.

The cellular stresses, genetic mutations, and environmental factors can critically affect the protein quality control checkpoints resulting in protein misfolding. Molecular chaperones play a crucial role in maintaining the healthy proteome by refolding the misfolded proteins into the native functional conformations. However, if they fail to refold the misfolded proteins into the native state, they are targeted by proteolytic systems for degradation.

IRGM restrains NLRP3 inflammasome activation by mediating its SQSTM1/p62-dependent selective autophagy.

IRGM is an established genetic risk factor for Crohn disease (CD) and several other inflammatory disorders. However, the mechanisms employed by IRGM to restrain the inflammation are not known. In our recent study, we showed that IRGM negatively regulates NLRP3 inflammasome activation.

TRIM16 governs the biogenesis and disposal of stress-induced protein aggregates to evade cytotoxicity: implication for neurodegeneration and cancer.

The formation of protein aggregates is linked to several diseases collectively called proteinopathies. The mechanisms and the molecular players that control the turnover of protein aggregates are not well defined. We recently showed that TRIM16 acts as a key regulatory protein to control the biogenesis and degradation of protein aggregates.

The Crohn's Disease Risk Factor IRGM Limits NLRP3 Inflammasome Activation by Impeding Its Assembly and by Mediating Its Selective Autophagy.

Several large-scale genome-wide association studies genetically linked IRGM to Crohn's disease and other inflammatory disorders in which the IRGM appears to have a protective function. However, the mechanism by which IRGM accomplishes this anti-inflammatory role remains unclear. Here, we reveal that IRGM/Irgm1 is a negative regulator of the NLRP3 inflammasome activation.

TRIM16 controls turnover of protein aggregates by modulating NRF2, ubiquitin system, and autophagy: implication for tumorigenesis.

Protein misfolding and protein aggregation are linked to several diseases commonly called as proteinopathies, which include cancer. Understanding the mechanisms of proteostasis could provide newer strategies to combat proteinopathies. We have recently demonstrated a new mechanism where we found that TRIM16 (tripartite motif-containing protein 16) utilizing NRF2-p62 axis and autophagy streamlines the safe disposal of misfolded proteins to maintain protein homeostasis.

TRIM16 controls assembly and degradation of protein aggregates by modulating the p62-NRF2 axis and autophagy.

Sequestration of protein aggregates in inclusion bodies and their subsequent degradation prevents proteostasis imbalance, cytotoxicity, and proteinopathies. The underlying molecular mechanisms controlling the turnover of protein aggregates are mostly uncharacterized. Herein, we show that a TRIM family protein, TRIM16, governs the process of stress-induced biogenesis and degradation of protein aggregates.

Sonorensin: A new bacteriocin with potential of an anti-biofilm agent and a food biopreservative.

The emergence of antibiotic resistant bacteria has led to exploration of alternative therapeutic agents such as ribosomally synthesized bacterial peptides known as bacteriocins. Biofilms, which are microbial communities that cause serious chronic infections, form environments that enhance antimicrobial resistance. Bacteria in biofilm can be upto thousand times more resistant to antibiotics than the same bacteria circulating in a planktonic state.

Bioprocess development for the production of sonorensin by Bacillus sonorensis MT93 and its application as a food preservative.

Media composition and environmental conditions were optimized using statistical tools, Plackett Burman design and response surface methodology, to maximize the yield of a bacteriocin, named as sonorensin, from a new marine isolate Bacillus sonorensis MT93 showing broad spectrum of antimicrobial activity. Under optimized conditions, MT93 produced 15-fold higher yield of sonorensin compared to that under initial fermentation conditions. As oxygen supply is a critical parameter controlling growth and product formation in aerobic bioprocesses and used as a parameter for bioprocess scale up, the effects of oxygen transfer, in terms of volumetric oxygen transfer coefficient (kLa), on production of sonorensin was investigated using optimized medium composition in a bioreactor.