RESUMEN
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.
Asunto(s)
Interleucina-2/administración & dosificación , Pulmón/inmunología , Organofosfatos/administración & dosificación , Peste/inmunología , Neumonía Bacteriana/inmunología , Receptores de Antígenos de Linfocitos T gamma-delta/inmunología , Linfocitos T/efectos de los fármacos , Yersinia pestis , Animales , Movimiento Celular , Modelos Animales de Enfermedad , Factor 7 de Crecimiento de Fibroblastos/biosíntesis , Homeostasis , Pulmón/microbiología , Pulmón/patología , Macaca , Peste/patología , Neumonía Bacteriana/patología , Mucosa Respiratoria/inmunología , Mucosa Respiratoria/microbiología , Mucosa Respiratoria/patología , Linfocitos T/inmunologíaRESUMEN
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.
Asunto(s)
Alelos , Escherichia coli/patogenicidad , Eliminación de Gen , Mutagénesis Sitio-Dirigida , Mutación , Electroforesis en Gel de Campo Pulsado , Escherichia coli/genética , Plásmidos/genética , Reacción en Cadena de la Polimerasa , Virulencia/genéticaRESUMEN
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.