Budesonide Suppresses Pulmonary Antibacterial Host Defense by Down- Regulating Cathelicidin-Related Antimicrobial Peptide

Antimicrobial peptides are a widespread component of host defense. We characterized the tissue distribution and cellular localization of expression of the magainin family of antimicrobial peptide genes in Xenopus laevis. Two genes from this family, magainin and PGLa, are expressed at high levels in the skin and throughout the gastrointestinal tract. Magainin and PGLa mRNAs are synthesized in the granular multinucleated cell (GMC) of the gastric mucosa, a cell shown previously to contain magainin and PGLa peptides by immunohistochemical methods. In addition, we have localized magainin and PGLa mRNAs to distinct cells of Xenopus small intestine. Further characterization of this large, granule-filled cell by electron microscopy demonstrates features in common with the Paneth cell of mammalian small intestine, previously identified as a site of expression of antimicrobial peptide genes of the defensin family in mouse and human. Our identification of granule-laden, eosinophilic intestinal cells in Xenopus as a site of magainin and PGLa antimicrobial peptide gene expression suggests that these cells are functional analogues of mammalian Paneth cells and further supports a conserved role of antimicrobial peptides in host defense of the vertebrate small intestine.

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Impaired Antibacterial Host Defense in Mice Lacking the N-formylpeptide Receptor

Journal of Experimental Medicine ◽

10.1084/jem.189.4.657 ◽

1999 ◽

Vol 189 (4) ◽

pp. 657-662 ◽

Cited By ~ 200

Author(s):

Ji-Liang Gao ◽

Eric J. Lee ◽

Philip M. Murphy

Keyword(s):

Host Defense ◽

Bacterial Load ◽

Direct Proof ◽

Specific Cellular Immune Response ◽

Specific Receptors ◽

Cellular Immune ◽

Antibacterial Host Defense ◽

Formylpeptide Receptor

N-formylpeptides derive from bacterial and mitochondrial proteins, and bind to specific receptors on mammalian phagocytes. Since binding induces chemotaxis and activation of phagocytes in vitro, it has been postulated that N-formylpeptide receptor signaling in vivo may be important in antimicrobial host defense, although direct proof has been lacking. Here we test this hypothesis in mice lacking the high affinity N-formylpeptide receptor (FPR), created by targeted gene disruption. FPR−/− mice developed normally, but had increased susceptibility to challenge with Listeria monocytogenes, as measured by increased mortality compared with wild-type littermates. FPR−/− mice also had increased bacterial load in spleen and liver 2 d after infection, which is before development of a specific cellular immune response, suggesting a defect in innate immunity. Consistent with this, neutrophil chemotaxis in vitro and neutrophil mobilization into peripheral blood in vivo in response to the prototype N-formylpeptide fMLF (formyl-methionyl-leucyl-phenylalanine) were both absent in FPR−/− mice. These results indicate that FPR functions in antibacterial host defense in vivo.

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Hormonal control of the renal immune response and antibacterial host defense by arginine vasopressin

Journal of Experimental Medicine ◽

10.1084/jem.20071032 ◽

2007 ◽

Vol 204 (12) ◽

pp. 2837-2852 ◽

Cited By ~ 46

Author(s):

Cécilia Chassin ◽

Mathias W. Hornef ◽

Marcelle Bens ◽

Michael Lotz ◽

Jean-Michel Goujon ◽

...

Keyword(s):

Immune Response ◽

Host Defense ◽

Arginine Vasopressin ◽

Hormonal Regulation ◽

Collecting Duct ◽

Hormonal Control ◽

Innate Immune ◽

Duct Cells ◽

Collecting Duct Cells ◽

Antibacterial Host Defense

Ascending urinary tract infection (UTI) and pyelonephritis caused by uropathogenic Escherichia coli (UPEC) are very common infections that can cause severe kidney damage. Collecting duct cells, the site of hormonally regulated ion transport and water absorption controlled by vasopressin, are the preferential intrarenal site of bacterial adhesion and initiation of inflammatory response. We investigated the effect of the potent V2 receptor (V2R) agonist deamino-8-D-arginine vasopressin (dDAVP) on the activation of the innate immune response using established and primary cultured collecting duct cells and an experimental model of ascending UTI. dDAVP inhibited Toll-like receptor 4–mediated nuclear factor κB activation and chemokine secretion in a V2R-specific manner. The dDAVP-mediated suppression involved activation of protein phosphatase 2A and required an intact cystic fibrosis transmembrane conductance regulator Cl− channel. In vivo infusion of dDAVP induced a marked fall in proinflammatory mediators and neutrophil recruitment, and a dramatic rise in the renal bacterial burden in mice inoculated with UPECs. Conversely, administration of the V2R antagonist SR121463B to UPEC-infected mice stimulated both the local innate response and the antibacterial host defense. These findings evidenced a novel hormonal regulation of innate immune cellular activation and demonstrate that dDAVP is a potent modulator of microbial-induced inflammation in the kidney.

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LSC Abstract – Interleukin-26 in antibacterial host defense of human lungs: Effects on neutrophil mobilization

10.1183/13993003.congress-2015.pa5110 ◽

2015 ◽

Author(s):

Karlhans Fru Che ◽

Sara Tengvall ◽

Bettina Levanen ◽

Elin Silverpil ◽

Margaretha Smith ◽

...

Keyword(s):

Host Defense ◽

Human Lungs ◽

Antibacterial Host Defense ◽

Interleukin 26

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SSD1 Is Integral to Host Defense Peptide Resistance in Candida albicans

Eukaryotic Cell ◽

10.1128/ec.00402-07 ◽

2008 ◽

Vol 7 (8) ◽

pp. 1318-1327 ◽

Cited By ~ 29

Author(s):

Kimberly D. Gank ◽

Michael R. Yeaman ◽

Satoshi Kojima ◽

Nannette Y. Yount ◽

Hyunsook Park ◽

...

Keyword(s):

Candida Albicans ◽

Antimicrobial Peptides ◽

Antimicrobial Peptide ◽

Host Defense ◽

Genomic Library ◽

Inflammatory Responses ◽

Host Defense Peptides ◽

Antimicrobial Peptide Resistance ◽

Null Mutants

ABSTRACT Candida albicans is usually a harmless human commensal. Because inflammatory responses are not normally induced by colonization, antimicrobial peptides are likely integral to first-line host defense against invasive candidiasis. Thus, C. albicans must have mechanisms to tolerate or circumvent molecular effectors of innate immunity and thereby colonize human tissues. Prior studies demonstrated that an antimicrobial peptide-resistant strain of C. albicans, 36082R, is hypervirulent in animal models versus its susceptible counterpart (36082S). The current study aimed to identify a genetic basis for antimicrobial peptide resistance in C. albicans. Screening of a C. albicans genomic library identified SSD1 as capable of conferring peptide resistance to a susceptible surrogate, Saccharomyces cerevisiae. Sequencing confirmed that the predicted translation products of 36082S and 36082R SSD1 genes were identical. However, Northern analyses corroborated that SSD1 is expressed at higher levels in 36082R than in 36082S. In isogenic backgrounds, ssd1Δ/ssd1Δ null mutants were significantly more susceptible to antimicrobial peptides than parental strains but had equivalent susceptibilities to nonpeptide stressors. Moreover, SSD1 complementation of ssd1Δ/ssd1Δ mutants restored parental antimicrobial peptide resistance phenotypes, and overexpression of SSD1 conferred enhanced peptide resistance. Consistent with these in vitro findings, ssd1 null mutants were significantly less virulent in a murine model of disseminated candidiasis than were their parental or complemented strains. Collectively, these results indicate that SSD1 is integral to C. albicans resistance to host defense peptides, a phenotype that appears to enhance the virulence of this organism in vivo.

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