Differential Outcome between BALB/c and C57BL/6 Mice after Escherichia coli O157:H7 Infection Is Associated with a Dissimilar Tolerance Mechanism

Abstract

Enterohemorrhagic Escherichia coli (EHEC) infections can result in a wide range of clinical presentations even though EHEC strain belongs to O157:H7 serotype, one of the most pathogenic ones. Although pathogen virulence influences disease outcome, we emphasize about the concept of host-pathogen interactions, which involve resistance or tolerance mechanisms in the host that finally determine host fitness and bacterial virulence. Taking advantage of the genetic differences between mouse strains, we analyzed the clinical progression in C57BL/6 and BALB/c weaned mice infected with an E. coli O157:H7 strain. We carefully analyzed colonization with several bacterial doses, clinical parameters, intestinal histology and the integrity of the intestinal barrier, as well as local and systemic levels of antibodies to pathogenic factors. We demonstrated that although both strains had comparable susceptibility to Shiga toxin (Stx) and the intestinal bacterial burden was similar, C57BL/6 showed increased intestinal damage and alteration of the integrity of the intestinal barrier, and impaired renal function that resulted in increased mortality. The increased survival rate in BALB/c strain was associated to an early specific antibody response as part of a tolerance mechanism.

Nasal immunization with H7 flagellin protects mice against hemolytic uremic syndrome secondary to Escherichia coli O157:H7 gastrointestinal infection

“…Several pieces of evidence support that protection against non-invasive enteric infections such as cholera and enterotoxigenic Escherichia coli (ETEC) diarrhea is mainly mediated through antigen-specific secretory IgA (SIgA) antibodies produced locally in the mucosa (Czerkinsky and Holmgren, 2015). Similarly, we recently demonstrated that protection against HUS associated with STEC-infection in mice is dependent on the B cell response and IgA specific antibodyresponse in the intestine (Bernal et al, 2021).…”

“…Control and FliC or H7-immunized mice were euthanized at day 6 p.i. with 125/99 pW strain to determine intestinal colonization as previously described ( Bernal et al., 2021 ). Briefly, 5 cm of the small and large intestine and the cecum were excised.…”

“…To measure the intestinal barrier function, a fluorescein isothiocyanate (FITC)- conjugated dextran (FITC-Dx; mean molecular weight 4 kDa) (Sigma-Aldrich, Oakville, ON, USA) assay was carried out as previously described ( Bernal et al., 2021 ). Briefly, 0.1 mL PBS containing 80 g/L FITC-Dx was orally administered at day 6 post 125/99 pW infection.…”

Prevention of Shiga toxin 1-caused colon injury by plant-derived recombinant IgA

“…As to several mucosal pathogens, it has been reported that pathogen-specific IgA can prevent infection 31 , 41 – 45 . As to Stx, previous studies indicated that mucosal vaccination could prevent disease and induce production of toxin-specific IgA antibodies, however, the effect of passively administered Stx-specific IgA was not clarified 33 , 39 , 46 . To examine the therapeutic effects of the plant-based IgA on oral administration, a sufficient amount of plantibody needs to be produced.…”

Braun Lipoprotein Protects against Escherichia coli-Induced Inflammatory Responses and Lethality in Mice

“…S3). In a previous study, both C57BL/6 and BALB/c mice were infected with E. coli , while C57BL/6 showed increased intestinal damage, altered integrity of the intestinal barrier, and impaired renal function that resulted in increased mortality ( 38 ). This phenomenon implies that it would be easier to observe BLP-induced tolerance in C57BL/6J mice than in other breeds.…”