Journal article
The host protein calprotectin modulates the Helicobacter pylori cag type IV secretion system via zinc sequestration
PLoS pathogens, Vol.10(10), pp.e1004450-e1004450
10/01/2014
DOI: 10.1371/journal.ppat.1004450
PMCID: PMC4199781
PMID: 25330071
Abstract
Transition metals are necessary for all forms of life including microorganisms, evidenced by the fact that 30% of all proteins are predicted to interact with a metal cofactor. Through a process termed nutritional immunity, the host actively sequesters essential nutrient metals away from invading pathogenic bacteria. Neutrophils participate in this process by producing several metal chelating proteins, including lactoferrin and calprotectin (CP). As neutrophils are an important component of the inflammatory response directed against the bacterium Helicobacter pylori, a major risk factor for gastric cancer, it was hypothesized that CP plays a role in the host response to H. pylori. Utilizing a murine model of H. pylori infection and gastric epithelial cell co-cultures, the role CP plays in modifying H. pylori -host interactions and the function of the cag Type IV Secretion System (cag T4SS) was investigated. This study indicates elevated gastric levels of CP are associated with the infiltration of neutrophils to the H. pylori-infected tissue. When infected with an H. pylori strain harboring a functional cag T4SS, calprotectin-deficient mice exhibited decreased bacterial burdens and a trend toward increased cag T4SS -dependent inflammation compared to wild-type mice. In vitro data demonstrate that culturing H. pylori with sub-inhibitory doses of CP reduces the activity of the cag T4SS and the biogenesis of cag T4SS-associated pili in a zinc-dependent fashion. Taken together, these data indicate that zinc homeostasis plays a role in regulating the proinflammatory activity of the cag T4SS.
Details
- Title: Subtitle
- The host protein calprotectin modulates the Helicobacter pylori cag type IV secretion system via zinc sequestration
- Creators
- Jennifer A Gaddy - Vanderbilt UniversityJana N Radin - Vanderbilt UniversityJohn T Loh - Vanderbilt UniversityM Blanca Piazuelo - Vanderbilt UniversityThomas E Kehl-Fie - Vanderbilt UniversityAlberto G Delgado - Vanderbilt UniversityFlorin T Ilca - Vanderbilt UniversityRichard M Peek - Vanderbilt UniversityTimothy L Cover - VA Tennessee Valley Healthcare SystemWalter J Chazin - Vanderbilt UniversityEric P Skaar - VA Tennessee Valley Healthcare SystemHolly M Scott Algood
- Resource Type
- Journal article
- Publication Details
- PLoS pathogens, Vol.10(10), pp.e1004450-e1004450
- DOI
- 10.1371/journal.ppat.1004450
- PMID
- 25330071
- PMCID
- PMC4199781
- ISSN
- 1553-7366
- eISSN
- 1553-7374
- Grant note
- P30 DK058404 / NIDDK NIH HHS IK2 BX001701 / BLRD VA R01 DK058587 / NIDDK NIH HHS CA 77955 / NCI NIH HHS K22 AI104805 / NIAID NIH HHS I01 BX000627 / BLRD VA P30DK058404 / NIDDK NIH HHS R29 CA077955 / NCI NIH HHS I01 BX000915 / BLRD VA P01 CA028842 / NCI NIH HHS R01 AI101171 / NIAID NIH HHS P01 CA116087 / NCI NIH HHS K22 AI104805-01 / NIAID NIH HHS DK 58587 / NIDDK NIH HHS T32 GM008320 / NIGMS NIH HHS R01 CA077955 / NCI NIH HHS R01 AI068009 / NIAID NIH HHS R01 AI039657 / NIAID NIH HHS
- Language
- English
- Date published
- 10/01/2014
- Academic Unit
- Microbiology and Immunology
- Record Identifier
- 9984618516302771
Metrics
5 Record Views