Selective effect of burn injury on splenic CD11c+ dendritic cells and CD8α+CD4−CD11c+ dendritic cell subsets

Patenaude, Johane; D’Elia, Michele; Hamelin, Claudine; Bernier, Jacques

doi:10.1007/s00018-009-0251-8

Cited by 16 publications

(9 citation statements)

References 64 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Other investigators have found that severe injury triggers DC dysfunction, which results in immune suppression. For example, Patenaude et al demonstrated that burn injury down-regulates TLR4/MD-2 expression on splenic CD11c + CD8α + cDCs and disrupts their TLR4 reactivity [32]. Kawasaki et al showed that severe injury attenuates the production of TNF-α, IL-6 and IFN-γ by cDCs [33].…”

Section: Discussionmentioning

confidence: 99%

Burn Injury Triggered Dysfunction in Dendritic Cell Response to TLR9 Activation and Resulted in Skewed T Cell Functions

et al. 2012

View full text Add to dashboard Cite

Severe trauma such as burn injury is often associated with a systemic inflammatory syndrome characterized by a hyperactive innate immune response and suppressed adaptive immune function. Dendritic cells (DCs), which sense pathogens via their Toll-like receptors (TLRs), play a pivotal role in protecting the host against infections. The effect of burn injury on TLR-mediated DC function is a debated topic and the mechanism controlling the purported immunosuppressive response remains to be elucidated. Here we examined the effects of burn injury on splenic conventional DC (cDC) and plasmacytoid DC (pDC) responses to TLR9 activation. We demonstrate that, following burn trauma, splenic cDCs’ cytokine production profile in response to TLR9 activation became anti-inflammatory dominant, with high production of IL-10 (>50% increase) and low production of IL-6, TNF-α and IL-12p70 (∼25–60% reduction). CD4+ T cells activated by these cDCs were defective in producing Th1 and Th17 cytokines. Furthermore, burn injury had a more accentuated effect on pDCs than on cDCs. Following TLR9 activation, pDCs displayed an immature phenotype with an impaired ability to secrete pro-inflammatory cytokines (IFN-α, IL-6 and TNF-α) and to activate T cell proliferation. Moreover, cDCs and pDCs from burn-injured mice had low transcript levels of TLR9 and several key molecules of the TLR signaling pathway. Although hyperactive innate immune response has been associated with severe injury, our data show to the contrary that DCs, as a key player in the innate immune system, had impaired TLR9 reactivity, an anti-inflammatory phenotype, and a dysfunctional T cell-priming ability. We conclude that burn injury induced impairments in DC immunobiology resulting in suppression of adaptive immune response. Targeted DC immunotherapies to promote their ability in triggering T cell immunity may represent a strategy to improve immune defenses against infection following burn injury.

show abstract

Section: Discussionmentioning

confidence: 99%

Burn Injury Triggered Dysfunction in Dendritic Cell Response to TLR9 Activation and Resulted in Skewed T Cell Functions

et al. 2012

View full text Add to dashboard Cite

show abstract

“…Several reports and our previous study have demonstrated that burn injury induced impairments in immunobiology of DCs, resulting in suppression of adaptive immune response [10, 11]. Patenaude also reported that burn injury caused a state of reprogramming DC subsets that were no longer capable of responding adequately to any subsequent challenge [12]. Moreover, a profound loss in the number of DCs, which mostly result from the apoptosis, was observed in spleen in burn injury as well as in sepsis [12–14].…”

Section: Introductionmentioning

confidence: 96%

“…Patenaude also reported that burn injury caused a state of reprogramming DC subsets that were no longer capable of responding adequately to any subsequent challenge [12]. Moreover, a profound loss in the number of DCs, which mostly result from the apoptosis, was observed in spleen in burn injury as well as in sepsis [12–14]. Functions of DCs could be influenced by endogenous signals and exogenous stimuli.…”

Section: Introductionmentioning

confidence: 99%

The involvement of endoplasmic reticulum stress response in immune dysfunction of dendritic cells after severe thermal injury in mice

et al. 2017

View full text Add to dashboard Cite

Suppressed adaptive immune function is one of the major concerns responsible for the development of opportunistic infections and subsequent sepsis with high mortality in severe burns. Endoplasmic reticulum stress (ERS) is the endogenous self-protective mechanism, and it plays an important role in almost every process of living by regulating the balance between homeostasis and apoptosis. The current study investigated the involvement of ERS in the pathogenesis of dysfunction of dendritic cells (DCs) in burn mice. Our results show a significant ERS response in splenic DC after burn injury. Treatment with salubrinal (Sal, reported to protect cells against ERS-induced apoptosis.) decrease the apoptotic rate of DC induced by burns, and promote maturation and activation of DC, as well as the ability to promote T cell proliferation and polarization towards Th1 immunity (all P<0.05). Gene silence of XBP-1 (key molecular in ERS response) results in the increased apoptosis and suppressed phenotypical maturation of splenic DC in burn mice. These results show that the excessive ERS is essential for immunosuppression during severe thermal injury. XBP-1 plays a pivotal role in DC functional immunomodulation in burn mice. Inhibition of apoptotic ERS response benefits mice from major burns.

show abstract

“…However differences in inflammatory signalling pathways in the two subsets remain poorly defined. Both have been reported to respond directly to LPS in vitro and in vivo, although they express relatively low basal levels of TLR4 [31], [32]. In vitro stimulation with LPS induces equivalent production of tumor necrosis factor alpha (TNFα) and IL-6, but higher production of IL-12 in CD8 DCs, suggesting that while both subsets share common signalling pathways and TLR4 potency, subset-specific differences are also present [31].…”

Section: Introductionmentioning

confidence: 99%

A Systems Biology Approach to the Analysis of Subset-Specific Responses to Lipopolysaccharide in Dendritic Cells

et al. 2014

View full text Add to dashboard Cite

Dendritic cells (DCs) are critical for regulating CD4 and CD8 T cell immunity, controlling Th1, Th2, and Th17 commitment, generating inducible Tregs, and mediating tolerance. It is believed that distinct DC subsets have evolved to control these different immune outcomes. However, how DC subsets mount different responses to inflammatory and/or tolerogenic signals in order to accomplish their divergent functions remains unclear. Lipopolysaccharide (LPS) provides an excellent model for investigating responses in closely related splenic DC subsets, as all subsets express the LPS receptor TLR4 and respond to LPS in vitro. However, previous studies of the LPS-induced DC transcriptome have been performed only on mixed DC populations. Moreover, comparisons of the in vivo response of two closely related DC subsets to LPS stimulation have not been reported in the literature to date. We compared the transcriptomes of murine splenic CD8 and CD11b DC subsets after in vivo LPS stimulation, using RNA-Seq and systems biology approaches. We identified subset-specific gene signatures, which included multiple functional immune mediators unique to each subset. To explain the observed subset-specific differences, we used a network analysis approach. While both DC subsets used a conserved set of transcription factors and major signalling pathways, the subsets showed differential regulation of sets of genes that ‘fine-tune’ the network Hubs expressed in common. We propose a model in which signalling through common pathway components is ‘fine-tuned’ by transcriptional control of subset-specific modulators, thus allowing for distinct functional outcomes in closely related DC subsets. We extend this analysis to comparable datasets from the literature and confirm that our model can account for cell subset-specific responses to LPS stimulation in multiple subpopulations in mouse and man.

show abstract

Selective effect of burn injury on splenic CD11c+ dendritic cells and CD8α+CD4−CD11c+ dendritic cell subsets

Cited by 16 publications

References 64 publications

Burn Injury Triggered Dysfunction in Dendritic Cell Response to TLR9 Activation and Resulted in Skewed T Cell Functions

Burn Injury Triggered Dysfunction in Dendritic Cell Response to TLR9 Activation and Resulted in Skewed T Cell Functions

The involvement of endoplasmic reticulum stress response in immune dysfunction of dendritic cells after severe thermal injury in mice

A Systems Biology Approach to the Analysis of Subset-Specific Responses to Lipopolysaccharide in Dendritic Cells

Contact Info

Product

Resources

About