Increased Percentages of T Helper Cells Producing IL-17 and Monocytes Expressing Markers of Alternative Activation in Patients with Sepsis

Brunialti, Milena Karina Coló; Santos, Manuel Lopes dos; Rigato, Otelo; Machado, Flávia Ribeiro; Silva, Eliezer; Salomão, Reinaldo

doi:10.1371/journal.pone.0037393

Cited by 50 publications

(40 citation statements)

References 54 publications

(73 reference statements)

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“…Conversely, sepsis-surviving mice lacking ST2 or STAT6 do not show polarization of M2-like macrophage, indicating that type 2 cytokines and IL-33 are critically involved in the polarization of M2 macrophages in sepsis-surviving mice. Consistent with this observation, increased number of circulating M2 macrophage was reported in septic patients43.…”

Section: Discussionsupporting

confidence: 78%

IL-33 contributes to sepsis-induced long-term immunosuppression by expanding the regulatory T cell population

et al. 2017

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Patients who survive sepsis can develop long-term immune dysfunction, with expansion of the regulatory T (Treg) cell population. However, how Treg cells proliferate in these patients is not clear. Here we show that IL-33 has a major function in the induction of this immunosuppression. Mice deficient in ST2 (IL-33R) develop attenuated immunosuppression in cases that survive sepsis, whereas treatment of naive wild-type mice with IL-33 induces immunosuppression. IL-33, released during tissue injury in sepsis, activates type 2 innate lymphoid cells, which promote polarization of M2 macrophages, thereby enhancing expansion of the Treg cell population via IL-10. Moreover, sepsis-surviving patients have more Treg cells, IL-33 and IL-10 in their peripheral blood. Our study suggests that targeting IL-33 may be an effective treatment for sepsis-induced immunosuppression.

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Section: Discussionsupporting

confidence: 78%

IL-33 contributes to sepsis-induced long-term immunosuppression by expanding the regulatory T cell population

et al. 2017

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“…These cells are CD14 high CD16 + , similar to the population described as “intermediate” monocytes [8]. However, they also express a marker of alternative monocyte/macrophage activation and differentiation, CD163 [15]. Our results implicate TGF-β and M-CSF in the differentiation of this subpopulation, and CRP as a potential activator of these cells for cytokine production.…”

Section: Discussionsupporting

confidence: 67%

“…These monocytes are the main producers of the anti-inflammatory cytokine IL-10 in response to LPS stimulation [11]. In addition these monocytes and “classical” monocytes when stimulated by alternative activation pathways express the CD163 hemoglobin scavenger receptor [15]. CD163 is responsible for clearance of hemoglobin-haptoglobin (Hb-Hp) complexes, mediating endocytosis of the complex, release of IL-10 and expression of HO-1 [11], [16], [17].…”

Section: Introductionmentioning

confidence: 99%

Transforming Growth Factor-β, Macrophage Colony-Stimulating Factor and C-Reactive Protein Levels Correlate with CD14highCD16+ Monocyte Induction and Activation in Trauma Patients

et al. 2012

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Severe injury remains a leading cause of death and morbidity in patients under 40, with the number of annual trauma-related deaths approaching 160,000 in the United States. Patients who survive the initial trauma and post-traumatic resuscitation are at risk for immune dysregulation, which contributes to late mortality and accounts for approximately 20% of deaths after traumatic injury. This post-traumatic immunosuppressed state has been attributed to over-expression of anti-inflammatory mediators in an effort to restore host homeostasis. We measured a panel of monocyte markers and cytokines in 50 severely injured trauma patients for 3 days following admission. We made the novel observation that the subpopulation of monocytes expressing high levels of CD14 and CD16 was expanded in the majority of patients. These cells also expressed CD163 consistent with differentiation into alternatively activated macrophages with potential regulatory or wound-healing activity. We examined factors in trauma plasma that may contribute to the generation and activation of these cells. The percentage of CD14highCD16+ monocytes after trauma correlated strongly with plasma C-reactive protein (CRP) transforming growth factor-β (TGF-β), and macrophage colony-stimulating factor (M-CSF) levels. We demonstrate a role for TGF-β and M-CSF, but not CRP in generating these cells using monocytes from healthy volunteers incubated with plasma from trauma patients. CD16 is a receptor for CRP and IgG, and we showed that monocytes differentiated to the CD14highCD16+ phenotype produced anti-inflammatory cytokines in response to acute phase concentrations of CRP. The role of these cells in immunosuppression following trauma is an area of ongoing investigation.

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“…Accordingly, the network analysis predicted differentiation of T lymphocytes as one of the functions modulated in septic patients. In our previous work, we found an increased proportion of Th17 cells and a decreased proportion of Th1 cells in septic patients in the context of decreased T lymphocyte cell numbers . We were unable to evaluate the expression of IL‐33, a member of the IL‐1 family which shows similarity to IL‐18 .…”

Section: Discussionmentioning

confidence: 87%

Inflammasome gene profile is modulated in septic patients, with a greater magnitude in non-survivors

Esquerdo

Sharma

Brunialti

et al. 2017

Clinical and Experimental Immunology

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Inflammasome signalling induces the processing and secretion of interleukin (IL)-1β and IL-18 which, coupled with pyroptosis, activate further the inflammatory response. In the present study we evaluated the expression of genes involved in inflammasome signalling pathways in septic patients, their interaction networks and the predicted functions modulated in survivors and non-survivors. Twenty-seven patients with sepsis secondary to community-acquired pneumonia admitted to intensive care units from three general hospitals in São Paulo were included into the study. We performed a polymerase chain reaction (PCR) array encompassing 35 genes related to the nucleotide-binding oligomerization domain and leucine-rich repeat-containing (NLR)-inflammasome in peripheral blood mononuclear cells obtained at admission and after 7 days of follow-up. Eleven healthy volunteers were used as the reference group. Increased NLRC4 and NLRP3 and decreased nucleotide-binding oligomerization domain (NOD1), and NLRP1 expression was observed in septic patients compared to healthy individuals; the IL-1β and IL-18 expression levels were also high in the patients. The gene expression changes followed the same patterns in surviving and non-surviving patients, with higher magnitudes observed in non-survivors. Functional analyses revealed, however, that activation and inhibition intensity for representing functions were different in survivors and non-survivors, as for production of reactive oxygen species, synthesis of nitric oxide and for the control of bacterial infections. Our results showed that the genes involved in the activation of the NLR-inflammasome cascades were altered substantially in septic patients, with a higher number of altered genes and a higher intensity in the disturbance of gene expression found among patients dying of sepsis.

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Increased Percentages of T Helper Cells Producing IL-17 and Monocytes Expressing Markers of Alternative Activation in Patients with Sepsis

Cited by 50 publications

References 54 publications

IL-33 contributes to sepsis-induced long-term immunosuppression by expanding the regulatory T cell population

IL-33 contributes to sepsis-induced long-term immunosuppression by expanding the regulatory T cell population

Transforming Growth Factor-β, Macrophage Colony-Stimulating Factor and C-Reactive Protein Levels Correlate with CD14highCD16+ Monocyte Induction and Activation in Trauma Patients

Inflammasome gene profile is modulated in septic patients, with a greater magnitude in non-survivors

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