title: The interleukin-17 receptor B subunit is essential for the Th2 response to Helicobacter pylori, but not for control of bacterial burden.
abstract: Helicobacter pylori infection leads to an inflammatory response in 100% of infected individuals. The inflammatory cells which are recruited to the gastric mucosa during infection produce several pro- and anti-inflammatory cytokines including several cytokines in the interleukin-17 family. The anti-inflammatory cytokine, interleukin 25 (IL-25, also known as IL-17E), signals through a receptor, which is a heterotrimeric receptor comprised of two IL-17 receptor A subunits and an IL-17 receptor B subunit. Previous studies in our laboratory demonstrated that IL-17RA is required to control infection with Helicobacter pylori in the mouse model. Moreover, the absence of IL-17 receptor A leads to a significant B cell infiltrate and a remarkable increase in lymphoid follicle formation in response to infection compared to infection in wild-type mice. We hypothesized that IL-25, which requires both IL-17 receptor A and IL-17 receptor B for signaling, may play a role in control of inflammation in the mouse model of Helicobacter pylori infection. IL-17 receptor B deficient mice, IL-17 receptor A deficient mice and wild-type mice were infected with Helicobacter pylori (strains SS1 and PMSS1). At several time points H. pylori-infected mice were sacrificed to investigate their ability to control infection and inflammation. Moreover, the effects of IL-17 receptor B deficiency on T helper cytokine expression and H. pylori- specific serum antibody responses were measured. IL-17 receptor B-/- mice (unlike IL-17 receptor A-/- mice) exhibited similar or modest changes in gastric colonization, inflammation, and Th1 and Th17 helper cytokine responses to wild-type mice infected with Helicobacter pylori. However, H. pylori-infected IL-17 receptor B-/- mice have reduced expression of IL-4 and lower serum IgG1 and IgG2a levels compared to infected IL-17 receptor A-/- and wild-type mice. These data indicate that signaling through the IL-17 receptor B subunit is not necessary for control of Helicobacter pylori in our model.
authors.affiliation: Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee, United States of America.
authors.forename: Dennis J
authors.initials: DJ
authors.lastname: Horvath
authors.forename: Jana N
authors.initials: JN
authors.lastname: Radin
authors.forename: Sung Hoon
authors.initials: SH
authors.lastname: Cho
authors.forename: M Kay
authors.initials: MK
authors.lastname: Washington
authors.forename: Holly M Scott
authors.initials: HM
authors.lastname: Algood
mesh_terms: D000818:Animals; D005260:Female; D005434:Flow Cytometry; D016481:Helicobacter Infections / Q000276:immunology*; D016480:Helicobacter pylori / Q000276:immunology* / Q000472:pathogenicity*; D020381:Interleukin-17 / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D053722:Receptors, Interleukin-17 / Q000737:chemistry / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013270:Stomach / Q000276:immunology / Q000382:microbiology
chemical_list: D020381:Interleukin-17; D053722:Receptors, Interleukin-17