ABSTRACT
The possibility that Vgamma2Vdelta2 T effector cells can confer protection against pulmonary infectious diseases has not been tested. We have recently demonstrated that single-dose (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate (HMBPP) plus IL-2 treatment can induce prolonged accumulation of Vgamma2Vdelta2 T effector cells in lungs. Here, we show that a delayed HMBPP/IL-2 administration after inhalational Yersinia pestis infection induced marked expansion of Vgamma2Vdelta2 T cells but failed to control extracellular plague bacterial replication/infection. Surprisingly, despite the absence of infection control, expansion of Vgamma2Vdelta2 T cells after HMBPP/IL-2 treatment led to the attenuation of inhalation plague lesions in lungs. Consistently, HMBPP-activated Vgamma2Vdelta2 T cells accumulated and localized in pulmonary interstitials surrounding small blood vessels and airway mucosa in the lung tissues with no or mild plague lesions. These infiltrating Vgamma2Vdelta2 T cells produced FGF-7, a homeostatic mediator against tissue damages. In contrast, control macaques treated with glucose plus IL-2 or glucose alone exhibited severe hemorrhages and necrosis in most lung lobes, with no or very few Vgamma2Vdelta2 T cells detectable in lung tissues. The findings are consist with the paradigm that circulating Vgamma2Vdelta2 T cells can traffic to lungs for homeostatic protection against tissue damages in infection.
Subject(s)
Interleukin-2/administration & dosage , Lung/immunology , Organophosphates/administration & dosage , Plague/immunology , Pneumonia, Bacterial/immunology , Receptors, Antigen, T-Cell, gamma-delta/immunology , T-Lymphocytes/drug effects , Yersinia pestis , Animals , Cell Movement , Disease Models, Animal , Fibroblast Growth Factor 7/biosynthesis , Homeostasis , Lung/microbiology , Lung/pathology , Macaca , Plague/pathology , Pneumonia, Bacterial/pathology , Respiratory Mucosa/immunology , Respiratory Mucosa/microbiology , Respiratory Mucosa/pathology , T-Lymphocytes/immunologyABSTRACT
Frequent unintended secondary mutations occurred in extraintestinal pathogenic Escherichia coli strains CP9, CFT073, and RS218 during suicide plasmid-mediated, putatively specific deletions of hlyA, papG allele III, and iha. Pulsed-field gel electrophoresis and PCR analyses demonstrated genomic alterations and/or unintended loss of defined virulence genes (papG, the F7-2 papA allele, iutA, sat, hlyD, and cnf). Caution is warranted when attributing the observed phenotypic changes to the intended mutation.
Subject(s)
Alleles , Escherichia coli/pathogenicity , Gene Deletion , Mutagenesis, Site-Directed , Mutation , Electrophoresis, Gel, Pulsed-Field , Escherichia coli/genetics , Plasmids/genetics , Polymerase Chain Reaction , Virulence/geneticsABSTRACT
Cell extracts from Yersinia pseudotuberculosis induced multinucleation in HEp-2 cells in a manner similar to the effect caused by Escherichia coli cytotoxic necrotizing factor (CNF). The activity was not dependent on the Yersinia 70-kb virulence plasmid, and the activity was not inhibited by antibodies capable of neutralizing E. coli CNF type 1. The nucleotide sequence of the Yersinia cnf gene was 65.1% identical to the E. coli cnf gene.
