Burn-injury affects gut-associated lymphoid tissues derived CD4+ T cells

Fazal, Nadeem; Shelip, Alla; Alzahrani, Alhusain J.

doi:10.1016/j.rinim.2013.09.001

Cited by 7 publications

(4 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In the gut, research has revealed increased intestinal epithelial apoptosis (7), as well as TJ breakdown secondary to thermal injury (8), thus attenuating the intestinal integrity. Furthermore, burn affects the gut immune homeostasis, and therefore the immune aspect of the intestinal barrier, as indicated by alterations in T-cell populations of intestinal origin (9). To add an extra layer of complexity to the dysregulation of the intestinal permeability following thermal injury, the aforementioned post-burn barrier alterations have been linked to dramatic shifts in the bacterial gut microbiome (10).…”

Section: Introductionmentioning

confidence: 99%

Targeting bacterial quorum sensing shows promise in improving intestinal barrier function following burn‑site infection

et al. 2019

View full text Add to dashboard Cite

Burn-site infections, commonly due to Pseudomonas aeruginosa , have been associated with deranged intestinal integrity, allowing bacteria and their products to translocate from the gut to the circulatory system. The P. aeruginosa quorum sensing (QS) transcription factor MvfR (PqsR) controls the expression of numerous virulence factors, and the synthesis of several toxic products. However, the role of QS in intestinal integrity alterations, to the best of our knowledge, has not been previously investigated. Using a proven anti-MvfR, anti-virulence agent, the in vivo results of the present study revealed that inhibition of MvfR function significantly decreased Fluorescein Isothiocyanate-Dextran (FITC-Dextran) flow from the intestine to the systemic circulation, diminished bacterial translocation from the intestine to mesenteric lymph nodes (MLNs), and improved tight junction integrity in thermally injured and infected mice. In addition, the MvfR antagonist administration alleviates the intestinal inflammation, as demonstrated by reduced ileal TNF-α and fecal lipocalin-2 concentrations. In addition, it is associated with lower levels of circulating endotoxin and decreased P. aeruginosa dissemination from the burn wound to the ileum. Collectively, these results hold great promise that the inhibition of this QS system mitigates gut hyperpermeability by attenuating the derangement of morphological and immune aspects of the intestinal barrier, suggesting that MvfR function is crucial in the deterioration of intestinal integrity following P. aeruginosa burn-site infection. Therefore, an anti-virulence approach targeting MvfR, could potentially offer a novel therapeutic approach against multi-drug resistant P. aeruginosa infections following thermal injuries. Since this approach is targeting virulence pathways that are non-essential for growth or viability, our strategy is hypothesized to minimize the development of bacterial resistance, and preserve the beneficial enteric microbes, while improving intestinal integrity that is deranged as a result of burn and infection.

show abstract

Section: Introductionmentioning

confidence: 99%

Targeting bacterial quorum sensing shows promise in improving intestinal barrier function following burn‑site infection

et al. 2019

View full text Add to dashboard Cite

show abstract

“…However, studies investigating suppressive capabilities of Tregs from burn-injured mice showed no difference in suppressive capability at day 1 post-injury and only noted increased suppressive capabilities at day 3 post-injury (48). Another study with adoptive transfer of Tregs isolated from day 3 post-injury rats into sham rats found that burninjured Tregs suppressed proliferation of PP and MLN CD4 T cells (49). In our model of ethanol intoxication combined with burn injury, we are able to see a significant difference in the suppression of effector T cell proliferation by Tregs isolated from injured mice at 24 h. As previously reported, effector T cells isolated from injured mice show poor proliferative responses compared to sham effector T cells in our suppression assays (22,29).…”

Section: Discussionmentioning

confidence: 99%

Ethanol Intoxication and Burn Injury Increases Intestinal Regulatory T Cell Population and Regulatory T Cell Suppressive Capability

Luck

Herrnreiter

et al. 2021

Shock

View full text Add to dashboard Cite

Traumatic injuries, such as burn, are often complicated by ethanol intoxication at the time of injury. This leads to a myriad of complications and post-burn pathologies exacerbated by aberrant immune responses. Recent findings suggest that immune cell dysfunction in the gastrointestinal system is particularly important in deleterious outcomes associated with burn injuries. In particular, intoxication at the time of burn injury leads to compromised intestinal T cell responses, which can diminish intestinal immunity and promote bacterial translocation, allowing for increased secondary infections in the injured host and associated sequelae, such as multiple organ failure and sepsis. Regulatory T cells (Treg) have been identified as important mediators of suppressing effector T cell function. Therefore, the goal of this study was to assess the effects of ethanol intoxication and burn injury on Treg populations in small intestinal immune organs. We also evaluated the suppressive capability of Tregs isolated from injured animals. Male C57BL/6 mice were gavaged with 2.9 g/kg ethanol before receiving a $12.5% total body surface area scald burn. One day after injury, we identified a significant increase in Tregs number in small intestine Peyer's patches ($Â1.5) and lamina propria ($Â2). Tregs-producing cytokine IL-10 were also increased in both tissues. Finally, Tregs isolated from ethanol and burn-injured mice were able to suppress proliferation of effector Tcells to a greater degree than sham vehicle Tregs. This was accompanied by increased levels of IL-10 and decreased levels of pro-proliferative cytokine IL-2 in cultures containing ethanol þ burn Tregs compared with sham Tregs. These findings suggest that Treg populations are increased in intestinal tissues 1 day following ethanol intoxication and burn injury. Tregs isolated from ethanol and burn-injured animals also exhibit a greater suppression of effector T cell proliferation, which may contribute to altered T cell responses following injury.

show abstract

“…ctla4 -cytotoxic t lymphocyte-associated antigen 4 -is expressed in t cells and delivers a negative signal to the primed lymphocyte, 85 directly antagonizing the costimulatory receptor cD28, and participating in t cell tolerance. ctla-4 expression is increased after burn injury, 86 after trauma-hemorrhage, 87,88 and in sepsis, and inhibits immune cell functions. 89 inoue et al showed a dosedependent effect of anti-ctla-4 on survival in a rodent model of sepsis, 90 with decreased cD8 + and cD4 + lymphocyte apoptosis.…”

Section: Cell Countsmentioning

confidence: 99%

Biological markers of injury-induced immunosuppression

Rouget¹,

Girardot²,

Textoris³

et al. 2017

Minerva Anestesiol

View full text Add to dashboard Cite

cal care medicine, mortality remains high and often not related to the initial injury, but rather to secondary events -especially infections -that occur during the immunosuppression period. 9 Mechanisms of this immunoparalysis and therapeutic opportunities have been recently published in the particular field of sepsis. 10 in the present review, we will focus on cellular biomarkers of injury-induced immunosuppression resulting from various forms of severe injuries. Unless specified, all studies cited in the present review involved intensive care patients. t he immune system response to major injuries often leads, after an initial hyperactivation, to an incompetent and hyporeactive immune status (Figure 1). this injury-induced immunosuppression has been described in the past decades in various clinical settings, such as septic shock, 1 severe trauma, 2 severe burns, 3 or major surgery. 4 When persistent or intense, immune paralysis is associated with the development of secondary infections and pejorative outcomes.

show abstract

Burn-injury affects gut-associated lymphoid tissues derived CD4+ T cells

Cited by 7 publications

References 30 publications

Targeting bacterial quorum sensing shows promise in improving intestinal barrier function following burn‑site infection

Targeting bacterial quorum sensing shows promise in improving intestinal barrier function following burn‑site infection

Ethanol Intoxication and Burn Injury Increases Intestinal Regulatory T Cell Population and Regulatory T Cell Suppressive Capability

Biological markers of injury-induced immunosuppression

Contact Info

Product

Resources

About