Cathelicidin in Skin Immunity

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Principal Investigator: Richard L Gallo
Organization: UNIVERSITY OF CALIFORNIA, SAN DIEGO
Fiscal Year: 2024
Award: $611,296
Funding agency: National Institute of Allergy and Infectious Diseases

PROJECT SUMMARY (See instructions):
This project has sought to understand the functions of the cathelicidin family of antimicrobial peptides in
mammalian immunity. Cathelicidins are an evolutionarily conserved gene family, with orthologous genes
present in several species. Conservation between family members resides primarily in the amino-terminal
precursor domain. The carboxy-terminal peptide domain has potent immunological activity, acting as an
endogenous direct antimicrobial that kills some pathogens. Our previous work has shown that this activity
is essential for resistance to invasive bacterial infection by S. aureus and Group A Streptococcus and
associated with several human inflammatory diseases. However, our group and others have found that
some of the human disease associations with cathelicidin are likely not a consequence of its antibiotic
activity but rather due to its immune activating activity. Several important observations prior to year 1
suggested that the human cathelicidin peptide LL37 will amplify inflammation by presenting nucleic acids
to cytosolic receptors. We termed this process " innate immune vetting " .

Terms: <2019 novel corona virus><2019 novel coronavirus><2019-nCoV><ATRA><Antibiotic Agents><Antibiotic Drugs><Antibiotic Therapy><Antibiotic Treatment><Antibiotics><Bacteria><Bacterial Infections><Blood leukocyte><Bone-Derived Transforming Growth Factor><CAP-18><CAP18><CAP18 lipopolysaccharide-binding protein><COVID-19 virus><COVID19 virus><CRAMP protein><Cell Communication and Signaling><Cell Signaling><Cnlp><CoV-2><CoV2><Coagulase><Coupled><Data><Disease><Disorder><Drug Synergism><Effectiveness><Elements><Endothelial Cells><Family><Family member><Fibroblasts><Gene Family><HIF 1><HIF-1 protein><HIF1><HIF1 protein><Host Defense><Human><IFN><Immune><Immunes><Immunity><Immunochemical Immunologic><Immunologic><Immunological><Immunologically><Immunologics><Immunomodulation><Infection><Inflammation><Inflammatory><Instruction><Interferons><Intracellular Communication and Signaling><Investigation><KI mice><Knock-in Mouse><LL37><Leukocytes><Leukocytes Reticuloendothelial System><Libraries><Ligand Binding><Lipids><Macrophage><Maps><Marrow leukocyte><Mice><Mice Mammals><Milk Growth Factor><Miscellaneous Antibiotic><Modern Man><Modification><Murine><Mus><Mφ><NT mimic 2><Non-Polyadenylated RNA><Nucleic Acids><Ortholog><Orthologous Gene><Parents><Pathogenicity Factors><Pathway interactions><Peptide Domain><Peptides><Physiologic><Physiological><Platelet Transforming Growth Factor><Process><Property><Protein Domains><RNA><RNA Gene Products><Research><Resistance><Retinoic Acid><Ribonucleic Acid><Role><S aureus><S pyogenes><S. aureus><S. pyogenes><SARS corona virus 2><SARS-CO-V2><SARS-COVID-2><SARS-CoV-2><SARS-CoV2><SARS-associated corona virus 2><SARS-associated coronavirus 2><SARS-coronavirus-2><SARS-related corona virus 2><SARS-related coronavirus 2><SARSCoV2><Sepsis><Severe Acute Respiratory Coronavirus 2><Severe Acute Respiratory Distress Syndrome CoV 2><Severe Acute Respiratory Distress Syndrome Corona Virus 2><Severe Acute Respiratory Distress Syndrome Coronavirus 2><Severe Acute Respiratory Syndrome CoV 2><Severe Acute Respiratory Syndrome-associated coronavirus 2><Severe Acute Respiratory Syndrome-related coronavirus 2><Severe acute respiratory syndrome associated corona virus 2><Severe acute respiratory syndrome coronavirus 2><Severe acute respiratory syndrome related corona virus 2><Signal Transduction><Signal Transduction Systems><Signaling><Skin><Staph aureus><Staphylococcus aureus><Streptococcus Group A><Streptococcus pyogenes><Structure><TGF B><TGF-beta><TGF-β><TGFbeta><TGFβ><Tertiary Protein Structure><Therapeutic><Trans Vitamin A Acid><Transforming Growth Factor beta><Transforming Growth Factor-Beta Family Gene><Tretinoin><Tretinoinum><UV induced><UV radiation-induced><Update><Virulence Factors><Vitamin A Acid><White Blood Cells><White Cell><Work><Wuhan coronavirus><acetyl-LDL receptor><acetylated LDL receptor><all-trans-Retinoic Acid><all-trans-Vitamin A acid><anti-microbial><anti-microbial peptide><antibiotic resistant pathogen><antimicrobial><bacteria infection><bacterial disease><bacterial disease treatment><bacterial infectious disease treatment><biological signal transduction><blood infection><bloodstream infection><cathelicidin><cathelicidin antimicrobial peptide><cathelin-like protein><cathelin-related antimicrobial peptide><coronavirus disease 2019 virus><coronavirus disease-19 virus><cytosolic receptor><drug repositioning><drug repurposing><drug resistant pathogen><gene conservation><hCoV19><human disease><hypoxia inducible factor 1><immune modulation><immune regulation><immunologic reactivity control><immunomodulatory><immunoregulation><immunoregulatory><in vivo><keratinocyte><knockin mice><mimic 2><mutant><nCoV2><neurotensin mimic 2><parent><pathogen><pathway><repurposing agent><repurposing medication><resistant><scavenger receptor><social role><synergism><trans-Retinoic Acid><ultraviolet induced><ultraviolet light induced><ultraviolet radiation-induced><uptake><white blood cell><white blood corpuscle>