Amino acid metabolism and signalling pathways: potential targets in the control of infection and immunity

Abstract

Defences to pathogens such as SarCoV2 in mammals involves interactions between immune functions and metabolic pathways to eradicate infection while preventing hyperinflammation. Amino acid metabolic pathways represent with other antimicrobial agent potential targets for therapeutic strategies. iNOS-mediated production of NO from Arg is involved in the innate inflammatory response to pathogens and NO overproduction can induce hyperinflammation. The two Arg-catabolising enzymes Arg1 and IDO1 reduce the hyperinflammation by an immunosuppressive effect via either Arg starvation (for Arg1) or via the immunoregulatory activity of the Arg-derived metabolites Kyn (for IDO1). In response to amino acid abundance mTOR activates the host protein translation and Coronaviruses use this machinery for their own protein synthesis and replication. In contrast GCN2, the sensor of amino acid starvation, activates pathways that restrict inflammation and viral replication. Gln depletion alters the immune response that become more suppressive, by favouring a regulatory T phenotype rather than a Th1 phenotype. Proliferating activated immune cells are highly dependent on Ser, activation and differentiation of T cells need enough Ser and dietary Ser restriction can inhibit their proliferation. Cys is strictly required for T-cell proliferation because they cannot convert Met to Cys. Restricting Met inhibits both viral RNA cap methylation and replication, and the proliferation of infected cells with an increased requirement for Met. Phe catabolism produces antimicrobial metabolites resulting in the inhibition of microbial growth and an immunosuppressive activity towards T lymphocytes.

L-amino-acids as immunity booster against COVID-19: DFT, molecular docking and MD simulations

“…We have mentioned that it can be an immunity booster so the possibility of infection due to nCoV will be less. [ 19 , 37 ]…”

“…Even, amino-acids the units of the proteins and so produces the antibodies in human to fight against the infection from SARS-CoV-2. [ 19 , 20 ] In the present work, authors have performed the DFT calculations of amino-acids and then their promising role in the inhibition of main protease of SARS-CoV-2 was investigated using molecular docking and molecular dynamics (MD) simulations.…”

Shared and Specific Lung Microbiota with Metabolic Profiles in Bronchoalveolar Lavage Fluid Between Infectious and Inflammatory Respiratory Diseases

“…Itaconic acid is derived from activated macrophages and can inhibit inflammation at low doses but promote inflammatory apoptosis at high doses. 47 Thus, in the HC group, the balanced composition of commensal flora may lead to relative amino acid starvation in the airway that could restrict viral invasion 11 and may also inhibit excessive inflammation. Once dysbiosis occurs in the LRT, depletion or abnormal enrichment of commensal flora will cause the host's original balanced immune state to be disrupted, and metabolic reprogramming of immune cells may also occur, causing invasion of pathogens and then an excessive inflammatory response.…”

“…Human microbial communities are typically complex and involve interactions between immune functions and metabolic pathways to eradicate infection while preventing hyperinflammation. [9][10][11] In healthy individuals, the composition of the airway microbiota is diverse, well balanced, and may comprise Prevotella, Streptococcus, and Veillonella, accompanied by other dynamically changing colonizers. 12 Many studies have found significant differences in the composition of the lung microbiome during lung diseases 13 and these diseases are generally associated with a loss of bacterial diversity or the dominance of a small group of taxa.…”

Gender-specific association of oxidative stress and immune response in septic shock mortality using NMR-based metabolomics

“…43 Arginine is a substrate for nitric oxide production required for the innate inflammatory response. 74 It is also necessary for normal T lymphocyte function, 75 and is known to have anti-inflammatory properties. 76 Another important attribute of the anti-inflammatory response in females is supported by the presence of carnitine and glycerol in their serum.…”