Brugia filariasis differentially modulates persistent Helicobacter pylori gastritis in the gerbil model.
In select Helicobacter pylori-infected populations with low gastric cancer, nematode coinfections are common and both helicobacter gastritis and filariasis are modeled in gerbils. We evaluated gastritis, worm counts, tissue cytokine gene expression levels and Th1/Th2-associated antibody responses in H. pylori and Brugia pahangi mono- and coinfected gerbils. H. pylori-associated gastritis indices were significantly lower 21 weeks post-infection in coinfected gerbils (p < or = 0.05) and were inversely proportional to worm counts (r(2) = -0.62, p < 0.003). Additionally, IFN-gamma, IL-1 beta, CXCL1, IL-4 and IL-10 mRNA levels in the gastric antrum reflected a significant host response to gastric H. pylori and as well as systemic filariasis (p < or = 0.05). Despite increasing worm burden (p < 0.05), gastritis progressed in coinfected gerbils (p < 0.03) becoming equivalent to H. pylori-infected gerbils at 42 weeks (p = 0.7). Pro- and anti-inflammatory mediator mRNA levels were notably downregulated in B. pahangi infected gerbils below uninfected control values, suggesting hyporesponsiveness to B. pahangi. Consistent with an increasing Th1 response to H. pylori, IgG2a (p < 0.01), IL-1 beta (p = 0.04) and CXCL1 (p = 0.006) responses significantly increased and IL-4 (p = 0.05) and IL-10 (p = 0.04) were decreased in coinfected gerbils at 42 weeks. Initial systemic responses to B. pahangi resulted in attenuated gastritis in coinfected gerbils, but subsequent filarid-associated hyporesponsiveness appears to have promoted H. pylori gastritis.
Martin
Heather R
HR
Division of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Shakya
Krishna P
KP
Muthupalani
Sureshkumar
S
Ge
Zhongming
Z
Klei
Thomas R
TR
Whary
Mark T
MT
Fox
James G
JG
D000818:Animals; D017179:Brugia pahangi / Q000276:immunology / Q000472:pathogenicity*; D016207:Cytokines / Q000096:biosynthesis; D004195:Disease Models, Animal; D005368:Filariasis / Q000276:immunology / Q000469:parasitology / Q000473:pathology*; D005753:Gastric Mucosa / Q000276:immunology / Q000473:pathology; D005756:Gastritis / Q000276:immunology / Q000382:microbiology / Q000473:pathology*; D020869:Gene Expression Profiling; D005849:Gerbillinae; D016481:Helicobacter Infections / Q000276:immunology / Q000382:microbiology / Q000473:pathology*; D016480:Helicobacter pylori / Q000276:immunology / Q000472:pathogenicity*; D006651:Histocytochemistry; D008853:Microscopy; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D012720:Severity of Illness Index
D016207:Cytokines; D012333:RNA, Messenger