Coinfection modulates inflammatory responses and clinical outcome of Helicobacter felis and Toxoplasma gondii infections.
The host immune response plays a critical role in determining disease manifestations of chronic infections. Inadequate immune response may fail to control infection, although in other cases the specific immune response may be the cause of tissue damage and disease. The majority of patients with chronic infections are infected by more than one organism yet the interaction between multiple active infections is not known, nor is the impact on disease outcome clear. Using the BALB/c strain of mice, we show that Toxoplasma gondii infection in a host infected with Helicobacter felis alters the natural outcome of T. gondii infection, allowing uncontrolled tachyzoite replication and severe organ damage. Survival rates decrease from 95% in T. gondii infection alone to 50% in dual-infected mice. In addition, infection with T. gondii alters the specific H. felis immune response, converting a previously resistant host to a susceptible phenotype. Gastric mucosal IFN-gamma and IL-12 were significantly elevated and IL-10 substantially reduced in dual-infected mice. These changes were associated with severe gastric mucosal inflammation, parietal cell loss, atrophy, and metaplastic cell changes. These data demonstrate the profound interactions between the immune response to unrelated organisms, and suggest these types of interactions my impact clinical disease.
Division of Gastroenterology, Department of Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA.
Calin
C
Stoicov
Mark
M
Whary
Arlin B
AB
Rogers
Frederick S
FS
Lee
Kristine
K
Klucevsek
Hanchen
H
Li
Xun
X
Cai
Reza
R
Saffari
Zhongming
Z
Ge
Imtiaz A
IA
Khan
Crescent
C
Combe
Andrew
A
Luster
James G
JG
Fox
JeanMarie
J
Houghton
D000818:Animals; D005753:Gastric Mucosa / Q000276:immunology / Q000382:microbiology; D005756:Gastritis / Q000276:immunology / Q000382:microbiology; D016481:Helicobacter Infections / Q000276:immunology* / Q000378:metabolism / Q000401:mortality / Q000503:physiopathology; D044922:Helicobacter felis / Q000276:immunology*; D007074:Immunoglobulin G / Q000235:genetics / Q000276:immunology; D007249:Inflammation / Q000276:immunology* / Q000503:physiopathology; D007371:Interferon-gamma / Q000378:metabolism; D008297:Male; D051379:Mice; D020033:Protein Isoforms / Q000235:genetics / Q000276:immunology; D014122:Toxoplasma / Q000276:immunology*; D014123:Toxoplasmosis / Q000276:immunology* / Q000378:metabolism / Q000401:mortality / Q000503:physiopathology
D007074:Immunoglobulin G; D020033:Protein Isoforms; D007371:Interferon-gamma