Abstract

Intestinal helminth infection can impair host resistance to co-infection with enteric bacterial pathogens. However, it is not known whether helminth drug-clearance can restore host resistance to bacterial infection. Using a mouse helminth-Salmonella co-infection system, we show that anthelmintic treatment prior to Salmonella challenge is sufficient to restore host resistance to Salmonella. The presence of the small intestine-dwelling helminth Heligmosomoides polygyrus at the point of Salmonella infection supports the initial establishment of Salmonella in the small intestinal lumen. Interestingly, if helminth drug-clearance is delayed until Salmonella has already established in the small intestinal lumen, anthelmintic treatment does not result in complete clearance of Salmonella. This suggests that while the presence of helminths supports initial Salmonella colonization, helminths are dispensable for Salmonella persistence in the host small intestine. These data contribute to the mechanistic understanding of how an ongoing or prior helminth infection can affect pathogenic bacterial colonization and persistence in the mammalian intestine.

Highlights

  • Helminths are parasitic worms that cause a significant global health concern [1]: it is estimated that more than one billion people are currently chronically infected with helminths

  • The current treatment for helminth infection is the administration of helminth-clearing drugs, yet it is not known whether drug clearance of helminths restores helminth-impaired host resistance to bacterial infection

  • In this report we use a mouse helminth-Salmonella coinfection model system, where we find that the presence of small intestinal helminths at the point of Salmonella infection aids the establishment of Salmonella in the small intestinal lumen

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Summary

Introduction

Helminths are parasitic worms that cause a significant global health concern [1]: it is estimated that more than one billion people are currently chronically infected with helminths. Helminth infection has been associated with impaired host resistance to co-infection with various pathogenic microbes, including bacterial pathogens, both in human populations [2,3,4,5,6] and in mouse models of co-infection [7,8,9,10,11,12,13,14,15,16,17]. It is not clear whether anthelmintic treatment is sufficient to restore host resistance to microbial pathogens.

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