The Regulation Of Anti-bacteria Innate Immune Responses By Heligmosomoides Polygyrus Infection

Helminths are estimated to infect3billion people worldwide. The distribution ofseveral helminth pathogens coincides geographically with many devastating microbialdiseases including HIV, malaria, and tuberculosis, and it is possible that the strongimmunomodulatory effects of helminthes on host responses may have a significantimpact on such coincident infections. In many developing countries, exposure tohelminth infections and simultaneous infection with other pathogens such as bacteriais very common.. Such as Salmonella enterica serovar Typhimurium (S.Typhimurium), it is a Gram-negative food-borne pathogen that is a major cause ofacute gastroenteritis in humans. The ability of the host to control such bacterialpathogens may be influenced by host immune status and by concurrent infections. Across-regulatory suppression of Th1responses by a helminth-driven strong Th2response has been suggested as a contributing factor to the alteration of the hostresponse to concurrent bacterial infections.Although much is known about thepotential role of helminth stimulated T cells, typically Th2and Treg, in altering hostprotection against the bacterial infection, the impact of helminth infection on theinnate immune response to enteric bacterial pathogens is less well understood. To testthe hypothesis that helminth infection may negatively regulate host mucosal innateimmunity against bacterial enteropathogens, a murine co-infection model wasestablished by using the intestinal nematode Heligmosomoides polygyrus and S.Typhimurium.In this study, Salmonella-induced acute colitis was used, and the bacterialevasion and output was calculated. Also the pathology and innate immune reponsesinclude monocyte recruitment, cytokine expressions and chemokine expressions weredetermined through the HE staining, FACs and Real-time PCR. The in vitrostimulation of macrophage by Th2cytokines and infection with Salmonella wasprocessed for understanding the mechanism of the way by which the helminthinfection suppresses the bacteria induced innate immune responses. We found that mice co-infected with S. Typhimurium and H. polygyrus developed more severeintestinal inflammation than animals infected with S. Typhimurium alone. Theenhanced susceptibility to Salmonella-induced intestinal injury in co-infected micewas found to be associated with diminished neutrophil recruitment to the site ofbacterial infection that correlated with decreased expression of the chemoattractantsMIP-2and KC, poor control of bacterial replication and exacerbated intestinalinflammation. The mechanism of helminth-induced inhibition of MIP-2and KCexpression involved IL-10and, to a less extent, IL-4and IL-13. Ly6G antibody-mediated depletion of neutrophils reproduced the adverse effects of H. polygyrus onSalmonella infection. Our results suggest that impaired neutrophil recruitment is animportant contributor to the enhanced severity of Salmonella enterocolitis associatedwith helminth co-infection. The Citrobacter rodentium (C. rodentium) infected micewith co-infected helminth H. polygyrus were used for verifying the impairedrecruitment of nrutrophil by the helminth infection. The results show the sameinbition of KC and Reg3γ in the conlon tissue from the co-infected mice withhelminth and bacteria. And the neutrophil recruitment was also suppressed by thehelminth infection.In the current study, we determined that the helminth infection may suppressesthe bacteria induced innate immune responses, and the helminth infection decreasesthe anti-microbial peptides, chemokine and cytokine expressions in the co-infectedmice with bacteria, failed the neutrophil recruitment during the innate immunityagainst bacteria. The better understanding of the regulation of helminth infection onthe innate immune responses induced by bacteria provides the novel insight and toolto prevent and control the co-current infection with helminth and bacteria.