Early immune innate hallmarks and microbiome changes across the gut during Escherichia coli O157: H7 infection in cattle

Mariano Larzábal,Nahuel A Riviere,Maia S Marin,Daniel A Vilte,Angel Cataldi,Lucas E Vagnoni,Dadin P Moore,Eduardo R Cobo,Wanderson Marques Da Silva,Matias Romero Victorica,Anmol Multani,Luo Le Guan,Tao Ma,Paola Talia,Fernando O Delgado

doi:10.1038/s41598-020-78752-x

Abstract

The zoonotic enterohemorrhagic Escherichia coli (EHEC) O157: H7 bacterium causes diarrhea, hemorrhagic colitis, and hemolytic uremic syndrome (HUS) in humans. Cattle are primary reservoirs and EHEC O157: H7; the bacteria predominately inhabit the colon and recto-anal junctions (RAJ). The early innate immune reactions in the infected gut are critical in the pathogenesis of EHEC O157: H7. In this study, calves orally inoculated with EHEC O157: H7 showed infiltration of neutrophils in the lamina propria of ileum and RAJ at 7 and 14 days post-infection. Infected calves had altered mucin layer and mast cell populations across small and large intestines. There were differential transcription expressions of key bovine β defensins, tracheal antimicrobial peptide (TAP) in the ileum, and lingual antimicrobial peptide (LAP) in RAJ. The main Gram-negative bacterial/LPS signaling Toll-Like receptor 4 (TLR4) was downregulated in RAJ. Intestinal infection with EHEC O157: H7 impacted the gut bacterial communities and influenced the relative abundance of Negativibacillus and Erysipelotrichaceae in mucosa-associated bacteria in the rectum. Thus, innate immunity in the gut of calves showed unique characteristics during infection with EHEC O157: H7, which occurred in the absence of major clinical manifestations but denoted an active immunological niche.

Highlights

The zoonotic enterohemorrhagic Escherichia coli (EHEC) O157: H7 bacterium causes diarrhea, hemorrhagic colitis, and hemolytic uremic syndrome (HUS) in humans
This study describes modifications in the gut innate immune defenses, including β-defensins tracheal antimicrobial peptide (TAP) and lingual antimicrobial peptide (LAP), IL8, and Toll-Like receptor 4 (TLR4) expression, the mucus layer, and the number of mast cells, in calves infected with and shedding EHEC O157: H7
The use of an EHEC O157: H7 (438/99) strain containing enterohemolysin, γ-intimin, type 3 secretion system (T3SS), Shiga toxins (Stx), and pO157 plasmid virulence factors may have contributed to its colonization[36,37,38,39,40] and the innate immune hallmarks, including the increased transcription of IL8 in the ileum and TLR4 in recto-anal junctions (RAJ) in infected calves in the early infection (7 d post-challenge)

Summary

Introduction

The zoonotic enterohemorrhagic Escherichia coli (EHEC) O157: H7 bacterium causes diarrhea, hemorrhagic colitis, and hemolytic uremic syndrome (HUS) in humans. EHEC inhabits the gastrointestinal tracts of humans and other homeothermic animals[3] In cattle, it colonizes the colon and persists in the rectum[5]. Reported functions of cathelicidins and β-defensins include bacterial killing and immunomodulatory functions such as chemotaxis of leukocytes, epithelial wound repair, and activation of chemokine secretion[12,14], infer their potential role in the innate immune defense against EHEC O157: H7. Whereas mast cell populations in the rectums of EHEC O157: H7 colonized calves were not different after 2 weeks of infection[32], how mast cells respond earlier during the infection onset is undetermined These innate gut defenses must coexist with the gut microbiota, which has implications on the exclusion of enteric p athogens[33] and livestock productivity[34]. To gain insights into the interactions between the gut innate immunity, microbiome, and EHEC O157: H7, this study aimed to explore early innate immune responses and bacterial communities in the intestinal tract of infected calves

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