Hemolytic uremic syndrome (HUS) is defined as a triad of noninmune microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury. The most frequent presentation is secondary to Shiga toxin (Stx)-producing Escherichia coli (STEC) infections, which is termed postdiarrheal, epidemiologic or Stx-HUS, considering that Stx is the necessary etiological factor. After ingestion, STEC colonize the intestine and produce Stx, which translocates across the intestinal epithelium. Once Stx enters the bloodstream, it interacts with renal endothelial and epithelial cells, and leukocytes. This review summarizes the current evidence about the involvement of inflammatory components as central pathogenic factors that could determine outcome of STEC infections. Intestinal inflammation may favor epithelial leakage and subsequent passage of Stx to the systemic circulation. Vascular damage triggered by Stx promotes not only release of thrombin and increased fibrin concentration but also production of cytokines and chemokines by endothelial cells. Recent evidence from animal models and patients strongly indicate that several immune cells types may participate in HUS physiopathology: neutrophils, through release of proteases and reactive oxygen species (ROS); monocytes/macrophages through secretion of cytokines and chemokines. In addition, high levels of Bb factor and soluble C5b-9 (sC5b-9) in plasma as well as complement factors adhered to platelet-leukocyte complexes, microparticles and microvesicles, suggest activation of the alternative pathway of complement. Thus, acute immune response secondary to STEC infection, the Stx stimulatory effect on different immune cells, and inflammatory stimulus secondary to endothelial damage all together converge to define a strong inflammatory status that worsens Stx toxicity and disease.
A complementary gene to LrSV2 for specific adult plant leaf rust resistance in wheat was mapped on chromosome 4BL, tightly linked to Lr12 / 31. LrSV2 is a race-specific adult plant leaf rust (Puccinia triticina) resistance gene on subdistal chromosome 3BS detected in the cross of the traditional Argentinean wheat (Triticum aestivum) variety Sinvalocho MA and the experimental line Gama6. The analysis of the cross of R46 [recombinant inbred line (RIL) derived from Sinvalocho MA carrying LrSV2 gene and the complementary gene Lrc-SV2 identified in the current paper] and the commercial variety Relmo Siriri (not carrying neither of these two genes) allowed the detection of the unlinked complementary gene Lrc-SV2 because the presence of one dominant allele of both is necessary to express the LrSV2-specific adult plant resistance. Lrc-SV2 was mapped within a 1-cM interval on chromosome 4BL using 100 RILs from the cross Sinvalocho MA × Purple Straw. This genetic system resembles the Lr27+31 seedling resistance reported in the Australian varieties Gatcher and Timgalen where interacting genes map at similar chromosomal positions. However, in high-resolution maps, Lr27 and LrSV2 were already mapped to adjacent intervals on 3BS and Lrc-SV2 map position on 4BL is distal to the reported Lr12/31-flanking microsatellites.
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.
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