Virulent<i>Salmonella enterica</i>Serovar Typhimurium Evades Adaptive Immunity by Preventing Dendritic Cells from Activating T Cells

Tobar, Jaime A.; Carreño, Leandro J.; Bueno, Susan M.; González, Pablo A.; Mora, Jorge E.; Quezada, Sergio A.; Kalergis, Alexis M.

doi:10.1128/iai.00063-06

Cited by 94 publications

(177 citation statements)

References 54 publications

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“…We initially investigated proteins that form the structural framework of SPI-2 because the expression of these virulence factors is controlled by host cell Nramp1, and they participate in impeding dendritic cell antigen presentation and CD4 + T-cell priming. 20,21,23 To determine the requirement for Salmonella SPI-2 in culling pathogen-specific CD4 + T cells, we compared the dynamics of adoptively transferred FliC-specific CD4 + T cells after co-infection with Lm-FliC and Salmonella containing targeted non-polar defects in ssaV, which encodes a structural component of the SPI-2 type III secretion system (strain HH109, STDSPI-2), or an isogenic strain of wild-type Salmonella (strain SL12023). 29,30 In striking contrast to the near complete elimination of FliC-specific CD4 + T cells after co-infection with wild-type Salmonella, FliC-specific CD45.1 + CD4 + T cells were maintained when STDSPI-2 was used for co-infection instead (Fig.…”

Section: Culling Of Activated Cd4 + T Cells Requires Spi-2 Encoded VImentioning

confidence: 99%

“…6,13,15,16 By extension, Salmonella-expressed virulence determinants inhibit the priming of naive CD4 + T cells, which coincides with their blunted activation within the first 2-3 weeks after infection. 6,[17][18][19][20][21] Hence, circumventing the activation of protective CD4 + T cells represents an important survival strategy used by Salmonella for establishing and maintaining persistent infection.…”

Section: Introductionmentioning

confidence: 99%

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Selective culling of high avidity antigen-specific CD4+ T cells after virulent Salmonella infection

Ertelt¹,

Johanns²,

Mysz

et al. 2011

Immunology

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Summary Typhoid fever is a persistent infection caused by host‐adapted Salmonella strains adept at circumventing immune‐mediated host defences. Given the importance of T cells in protection, the culling of activated CD4+ T cells after primary infection has been proposed as a potential immune evasion strategy used by this pathogen. We demonstrate that the purging of activated antigen‐specific CD4+ T cells after virulent Salmonella infection requires SPI‐2 encoded virulence determinants, and is not restricted only to cells with specificity to Salmonella‐expressed antigens, but extends to CD4+ T cells primed to expand by co‐infection with recombinant Listeria monocytogenes. Unexpectedly, however, the loss of activated CD4+ T cells during Salmonella infection demonstrated using a monoclonal population of adoptively transferred CD4+ T cells was not reproduced among the endogenous repertoire of antigen‐specific CD4+ T cells identified with MHC class II tetramer. Analysis of T‐cell receptor variable segment usage revealed the selective loss and reciprocal enrichment of defined CD4+ T‐cell subsets after Salmonella co‐infection that is associated with the purging of antigen‐specific cells with the highest intensity of tetramer staining. Hence, virulent Salmonella triggers the selective culling of high avidity activated CD4+ T‐cell subsets, which re‐shapes the repertoire of antigen‐specific T cells that persist later after infection.

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Section: Culling Of Activated Cd4 + T Cells Requires Spi-2 Encoded VImentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Selective culling of high avidity antigen-specific CD4+ T cells after virulent Salmonella infection

Ertelt¹,

Johanns²,

Mysz

et al. 2011

Immunology

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“…[8][9][10][11][12] Dendritic cells (DCs) are professional antigen-presenting cells with the unique capacity to activate naive T cells, which later will exert an anti-viral immune response. [13][14][15] Priming of T cells requires DCs to efficiently capture and present viral proteins as antigenic peptide-MHC complexes and to provide co-stimulatory signals needed for full T-cell activation. These stimulating ligands are provided to T cells through the assembly of an immunological synapse (IS) between DCs and T cells.…”

Section: Introductionmentioning

confidence: 99%

Human metapneumovirus keeps dendritic cells from priming antigen‐specific naive T cells

2013

Self Cite

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SummaryHuman metapneumovirus (hMPV) is the second most common cause of acute lower respiratory tract infections in children, causing a significant public health burden worldwide. Given that hMPV can repeatedly infect the host without major antigenic changes, it has been suggested that hMPV may have evolved molecular mechanisms to impair host adaptive immunity and, more specifically, T-cell memory. Recent studies have shown that hMPV can interfere with superantigen-induced T-cell activation by infecting conventional dendritic cells (DCs). Here, we show that hMPV infects mouse DCs in a restricted manner and induces moderate maturation. Nonetheless, hMPV-infected DCs are rendered inefficient at activating naive antigen-specific CD4 + T cells (OT-II), which not only display reduced proliferation, but also show a marked reduction in surface activation markers and interleukin-2 secretion. Decreased T-cell activation was not mediated by interference with DC-T-cell immunological synapse formation as recently described for the human respiratory syncytial virus (hRSV), but rather by soluble factors secreted by hMPV-infected DCs. These data suggest that although hMPV infection is restricted within DCs, it is sufficient to interfere with their capacity to activate naive T cells. Altogether, by interfering with DC function and productive priming of antigen-inexperienced T cells, hMPV could impair the generation of long-term immunity.

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“…Successful bacterial pathogens have thus evolved strategies to mask these virulence factors from detection or to blunt the host response that is initiated (72)(73)(74). Indeed, a number of studies in several different systems have revealed that immune sensing of virulence factor activity promotes pathogen clearance (36,(75)(76)(77)(78)(79).…”

Section: Discussionmentioning

confidence: 99%

Guanylate Binding Proteins Regulate Inflammasome Activation in Response to Hyperinjected Yersinia Translocon Components

et al. 2017

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Gram-negative bacterial pathogens utilize virulence-associated secretion systems to inject, or translocate, effector proteins into host cells to manipulate cellular processes and promote bacterial replication. However, translocated bacterial products are sensed by nucleotide binding domain and leucine-rich repeat-containing proteins (NLRs), which trigger the formation of a multiprotein complex called the inflammasome, leading to secretion of interleukin-1 (IL-1) family cytokines, pyroptosis, and control of pathogen replication. Pathogenic Yersinia bacteria inject effector proteins termed Yops, as well as pore-forming proteins that comprise the translocon itself, into target cells. The Yersinia translocation regulatory protein YopK promotes bacterial virulence by limiting hyperinjection of the translocon proteins YopD and YopB into cells, thereby limiting cellular detection of Yersinia virulence activity. How hyperinjection of translocon proteins leads to inflammasome activation is currently unknown. We found that translocated YopB and YopD colocalized with the late endosomal/lysosomal protein LAMP1 and that the frequency of YopD and LAMP1 association correlated with the level of caspase-1 activation in individual cells. We also observed colocalization between YopD and Galectin-3, an indicator of endosomal membrane damage. Intriguingly, YopK limited the colocalization of Galectin-3 with YopD, suggesting that YopK limits the induction or sensing of endosomal membrane damage by components of the type III secretion system (T3SS) translocon. Furthermore, guanylate binding proteins (GBPs) encoded on chromosome 3 (Gbp Chr3 ), which respond to pathogen-induced damage or alteration of host membranes, were necessary for inflammasome activation in response to hyperinjected YopB/-D. Our findings indicate that lysosomal damage by Yersinia translocon proteins promotes inflammasome activation and implicate GBPs as key regulators of this process.

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VirulentSalmonella entericaSerovar Typhimurium Evades Adaptive Immunity by Preventing Dendritic Cells from Activating T Cells

Cited by 94 publications

References 54 publications

Selective culling of high avidity antigen-specific CD4+ T cells after virulent Salmonella infection

Selective culling of high avidity antigen-specific CD4+ T cells after virulent Salmonella infection

Human metapneumovirus keeps dendritic cells from priming antigen‐specific naive T cells

Guanylate Binding Proteins Regulate Inflammasome Activation in Response to Hyperinjected Yersinia Translocon Components

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