Impaired host resistance to Salmonella during helminth co-infection is restored by anthelmintic treatment prior to bacterial challenge
Autor: | Dongju Shin, Brandon E. Moeller, Katherine M Lawrence, Lisa A. Reynolds, Mia H E Kennedy, Courtney M. Gauthier, Kate M. E. Conway, Dominique M. Gatti, Rachael D. FitzPatrick, Tara P. Brosschot |
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Rok vydání: | 2021 |
Předmět: |
Male
Bacterial Diseases 0301 basic medicine Salmonella Salmonellosis RC955-962 Helminthiasis Salmonella infection Pathology and Laboratory Medicine medicine.disease_cause Mice fluids and secretions Medical Conditions 0302 clinical medicine Arctic medicine. Tropical medicine Medicine and Health Sciences Colonization Anthelmintic Intestinal Diseases Parasitic Helminthic therapy Disease Resistance Mice Inbred BALB C Nematospiroides dubius biology Coinfection Eukaryota Bacterial Pathogens 3. Good health Intestines Infectious Diseases medicine.anatomical_structure Medical Microbiology Helminth Infections Salmonella Infections Salmonella Typhimurium Small Intestine Female Immunotherapy Public aspects of medicine RA1-1270 Pathogens Anatomy Research Article medicine.drug Immunology 030231 tropical medicine Microbiology 03 medical and health sciences Enterobacteriaceae Helminths parasitic diseases Parasitic Diseases medicine Animals Microbial Pathogens Bacteria Organisms Public Health Environmental and Occupational Health Biology and Life Sciences Salmonella typhi biology.organism_classification medicine.disease Invertebrates Small intestine Gastrointestinal Microbiome Helminthic Therapy Mice Inbred C57BL Gastrointestinal Tract Disease Models Animal 030104 developmental biology Clinical Immunology Heligmosomoides polygyrus Clinical Medicine Zoology Digestive System |
Zdroj: | PLoS Neglected Tropical Diseases PLoS Neglected Tropical Diseases, Vol 15, Iss 1, p e0009052 (2021) |
ISSN: | 1935-2735 |
Popis: | 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. Author summary In regions where helminth infection is common and sanitation standards are poor, people are at a high risk of exposure to bacterial pathogens. Previous work in animal models has shown that helminth infection can impair host resistance to bacterial infection. 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 co-infection 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. We show that helminth drug clearance prior to Salmonella infection is sufficient to restore host resistance to Salmonella. However, if helminth drug clearance is delayed until after Salmonella had already established in the small intestinal lumen, helminth elimination does not result in complete clearance of Salmonella from this site. Our work suggests that helminth drug clearance may be beneficial in reducing susceptibility to subsequent intestinal bacterial infections, but that helminth drug clearance after co-infection may not result in clearance of bacterial populations that have firmly established in the intestinal lumen. |
Databáze: | OpenAIRE |
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