13 research outputs found
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The flagellar regulator TviA reduces pyroptosis by Salmonella enterica serovar Typhi.
To discern virulent from innocuous microbes, the innate immune system senses events associated with bacterial access to immunoprivileged sites such as the host cell cytosol. One such pathway is triggered by the cytosolic delivery of flagellin, the major subunit of the flagellum, by bacterial secretion systems. This leads to inflammasome activation and subsequent proinflammatory cell death (pyroptosis) of the infected phagocyte. In this study, we demonstrate that the causative agent of typhoid fever, Salmonella enterica serovar Typhi, can partially subvert this critical innate immune recognition event. The transcriptional regulator TviA, which is absent from Salmonella serovars associated with human gastroenteritis, repressed the expression of flagellin during infection of human macrophage-like (THP-1) cells. This mechanism allowed S. Typhi to dampen inflammasome activation, leading to reduced interleukin-1β (IL-1β) secretion and diminished cell death. Likewise, the introduction of the tviA gene in nontyphoidal Salmonella enterica serovar Typhimurium reduced flagellin-induced pyroptosis. These data suggest that gene regulation of virulence factors enables S. Typhi to evade innate immune recognition by concealing a pathogen-induced process from being sensed by the inflammasome
The flagellar regulator TviA reduces pyroptosis by Salmonella enterica serovar Typhi.
To discern virulent from innocuous microbes, the innate immune system senses events associated with bacterial access to immunoprivileged sites such as the host cell cytosol. One such pathway is triggered by the cytosolic delivery of flagellin, the major subunit of the flagellum, by bacterial secretion systems. This leads to inflammasome activation and subsequent proinflammatory cell death (pyroptosis) of the infected phagocyte. In this study, we demonstrate that the causative agent of typhoid fever, Salmonella enterica serovar Typhi, can partially subvert this critical innate immune recognition event. The transcriptional regulator TviA, which is absent from Salmonella serovars associated with human gastroenteritis, repressed the expression of flagellin during infection of human macrophage-like (THP-1) cells. This mechanism allowed S. Typhi to dampen inflammasome activation, leading to reduced interleukin-1β (IL-1β) secretion and diminished cell death. Likewise, the introduction of the tviA gene in nontyphoidal Salmonella enterica serovar Typhimurium reduced flagellin-induced pyroptosis. These data suggest that gene regulation of virulence factors enables S. Typhi to evade innate immune recognition by concealing a pathogen-induced process from being sensed by the inflammasome
Frequency of isolation of wild type <i>Brucella ovis</i> from semen (A) and urine (B); or PCR detection in semen (C) or urine (D) samples, before and after challenge.
<p>The number of weeks is indicated in the x axis.</p
Microscopic changes in the reproductive system of non immunized rams experimentally challenged with <i>Brucella ovis</i>, at 8 weeks post challenge.
<p>Severe neutrophilic epididymitis associated to cystic epithelium degeneration (black arrow), with positive immunestaining for <i>B</i>. <i>ovis</i> (inset, 100X) in the tail of the epididymis from a non immunized ram (A). Tail of the epididymis from a ram immunized with encapsulated <i>B</i>. <i>ovis</i> Δ<i>abcBA</i> and challenged with wild type <i>B</i>. <i>ovis</i> with no histological changes (B). Moderate lympho-histiocytic and neutrophilic inflammatory infiltrate in the ampullae of a non immunized ram (C). Absence of histological changes in the ampullae of a ram immunized with encapsulated <i>B</i>. <i>ovis</i> Δ<i>abcBA</i> and challenged with wild type <i>B</i>. <i>ovis</i> (D), H. E. Bar = 50 μm.</p
Frequency of seropositive rams (non immunized or immunized with encapsulated or non encapsulated <i>Brucella ovis</i> Δ<i>abcBA</i>).
<p>Seropositivity was determined by agar gel immune diffusion (AGID) before and after challenge. The number of weeks before and after challenge is indicated in the x axis. Statistical differences between groups (10 rams per group) are indicated by asterisks (**p<0.01; *** p<0.001).</p
Peripheral blood leukocyte immunophenotyping of non immunized rams, and rams immunized with encapsulated or non encapsulated <i>B</i>. <i>ovis</i> Δ<i>abcBA</i>.
<p>Samples were obtained prior to immunization, 1 and 4 weeks after immunization, and 1 and 4 weeks after challenge. (A) CD4<sup>+</sup> T lymphocytes, (B) CD8<sup>+</sup> T lymphocytes, (C) γ/Δ T lymphocytes, and (D) B lymphocytes. The number of weeks before and after challenge is indicated in the x axis. Data represents mean and standard error.</p
Gross lesions in the reproductive system of non immunized rams experimentally challenged with wild type <i>Brucella ovis</i>, at 8 weeks post infection.
<p>Asymmetry of the tail of the epididymis (A). Granuloma between the visceral and parietal layers of the tunica vaginalis, adjacent to the tail of the epididymis (black arrow) (B). Fibrous adhesion between testis and the head of the epididymis (black arrow) (C). Fibrinous adhesion on the tunica vaginalis (black arrow) (D).</p
Frequency of isolation (A) or PCR detection (B) of wild type <i>Brucella ovis</i> in tissues from non immunized rams or rams immunized with encapsulated or non encapsulated <i>Brucella ovis</i> Δ<i>abcBA</i> at eight weeks post experimental challenge with wild type <i>B</i>. <i>ovis</i>.
<p>Frequency of isolation (A) or PCR detection (B) of wild type <i>Brucella ovis</i> in tissues from non immunized rams or rams immunized with encapsulated or non encapsulated <i>Brucella ovis</i> Δ<i>abcBA</i> at eight weeks post experimental challenge with wild type <i>B</i>. <i>ovis</i>.</p
Encapsulated <i>Brucella ovis</i> Lacking a Putative ATP-Binding Cassette Transporter (Δ<i>abcBA</i>) Protects against Wild Type <i>Brucella ovis - Fig 1 </i> in Rams
<p>Scanning electron micrograph of alginate capsules, Bar = 100 μm (A); detail of the surface of the capsule (B); fluorescence microscopy of alginate capsules containing <i>mCherry</i>-expressing <i>Brucella ovis</i> Δ<i>abcBA</i>, Bar = 100 μm (C). Higher magnification demonstrating individualized <i>mCherry</i>-expressing <i>Brucella ovis</i> Δ<i>abcBA</i> (D).</p
Lymphocyte proliferation assay at 8 weeks post immunization (A) and 8 weeks post challenge (B) in non immunized rams, and rams immunized with encapsulated or non encapsulated <i>Brucella ovis</i> Δ<i>abcBA</i>.
<p>Columns represent the mean of 10 rams. Data represent mean and standard error. Asterisks indicate statistical differences between groups (* p<0.05; ** p<0.01).</p