Differences in monocyte subsets are associated with short‐term survival in patients with septic shock

Hortová-Kohoutková, Marcela; Lázničková, Petra; Bendíčková, Kamila; Zuani, Marco De; Andrejčinová, Ivana; Tomášková, Veronika; Suk, Pavel; Šrámek, Vladimír; Helán, Martin; Frič, Jan

doi:10.1111/jcmm.15791

Cited by 18 publications

(18 citation statements)

References 42 publications

(72 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In sharp contrast, the expression of PD-L1 was not tolerized, and continually induced in monocytes following repetitive LPS challenge at day 3 and day 5 time points compared to PBS controls (Figure 1C and Supplementary Figure S1C). Collectively, our in vitro system of repetitive LPS challenges for a 5-day time period generated a representative monocyte exhaustion phenotype with reduced expression of MHCII and co-stimulatory molecule CD86, as well as continued induction of immuno-suppressor PD-L1, consistent with the exhausted monocyte phenotype observed in experimental animals and human sepsis patients (29)(30)(31). We therefore used the 5-day culture system to further characterize the exhausted monocytes in this study.…”

Section: Generation Of Exhausted Monocytes With Prolonged and Repetitive Treatments Of High Dose Lpsmentioning

confidence: 88%

Development of Exhausted Memory Monocytes and Underlying Mechanisms

Pradhan

Geng

et al. 2021

Front. Immunol.

View full text Add to dashboard Cite

Pathogenic inflammation and immuno-suppression are cardinal features of exhausted monocytes increasingly recognized in septic patients and murine models of sepsis. However, underlying mechanisms responsible for the generation of exhausted monocytes have not been addressed. In this report, we examined the generation of exhausted primary murine monocytes through prolonged and repetitive challenges with high dose bacterial endotoxin lipopolysaccharide (LPS). We demonstrated that repetitive LPS challenges skew monocytes into the classically exhausted Ly6Chi population, and deplete the homeostatic non-classical Ly6Clo population, reminiscent of monocyte exhaustion in septic patients. scRNAseq analyses confirmed the expansion of Ly6Chi monocyte cluster, with elevation of pathogenic inflammatory genes previously observed in human septic patients. Furthermore, we identified CD38 as an inflammatory mediator of exhausted monocytes, associated with a drastic depletion of cellular NAD+; elevation of ROS; and compromise of mitochondria respiration, representative of septic monocytes. Mechanistically, we revealed that STAT1 is robustly elevated and sustained in LPS-exhausted monocytes, dependent upon the TRAM adaptor of the TLR4 pathway. TRAM deficient monocytes are largely resistant to LPS-mediated exhaustion, and retain the non-classical homeostatic features. Together, our current study addresses an important yet less-examined area of monocyte exhaustion, by providing phenotypic and mechanistic insights regarding the generation of exhausted monocytes.

show abstract

Section: Generation Of Exhausted Monocytes With Prolonged and Repetitive Treatments Of High Dose Lpsmentioning

confidence: 88%

Development of Exhausted Memory Monocytes and Underlying Mechanisms

Pradhan

Geng

et al. 2021

Front. Immunol.

View full text Add to dashboard Cite

show abstract

“…Monocytes represent the first line of defense against invading pathogens. They are activated by pattern recognition receptors (PRRs) and sepsis-associated hypoxia [31]. Monocytes control both the innate and adaptive immune responses to pathogens by different mechanisms, including phagocytosis; the release of reactive oxygen species, cytokines, and chemokines; the recruiting of neutrophils; antigen presentation; and the activation of lymphocytes [32].…”

Section: Monocytesmentioning

confidence: 99%

The Value of a Complete Blood Count (CBC) for Sepsis Diagnosis and Prognosis

et al. 2021

View full text Add to dashboard Cite

Sepsis represents an important global health burden due to its high mortality and morbidity. The rapid detection of sepsis is crucial in order to prevent adverse outcomes and reduce mortality. However, the diagnosis of sepsis is still challenging and many efforts have been made to identify reliable biomarkers. Unfortunately, many investigated biomarkers have several limitations that do not support their introduction in clinical practice, such as moderate diagnostic and prognostic accuracy, long turn-around time, and high-costs. Complete blood count represents instead a precious test that provides a wealth of information on individual health status. It can guide clinicians to early-identify patients at high risk of developing sepsis and to predict adverse outcomes. It has several advantages, being cheap, easy-to-perform, and available in all wards, from the emergency department to the intensive care unit. Noteworthy, it represents a first-level test and an alteration of its parameters must always be considered within the clinical context, and the eventual suspect of sepsis must be confirmed by more specific investigations. In this review, we describe the usefulness of basic and new complete blood count parameters as diagnostic and prognostic biomarkers of sepsis.

show abstract

“…Stimulation of monocytes by LPS increases the expression of TLR4, leading to the generation of inflammatory molecules. These proinflammatory factors have an important role in inflammatory diseases [ 21 ], including atherosclerosis [ 24 ], rheumatoid arthritis [ 25 ], and sepsis [ 26 ]. Thus, it is emphasized to find a pharmacological compound that does not have cytotoxicity and undesirable effects and exhibits such anti-inflammatory effects.…”

Section: Resultsmentioning

confidence: 99%

Anti-Inflammatory Effects of the Fraction from the Leaves of Pyrus pyrifolia on LPS-Stimulated THP-1 Cells

Lee

Kim

Jang

et al. 2021

Evidence-Based Complementary and Alternative Medicine

View full text Add to dashboard Cite

Pyrus pyrifolia Nakai (P. pyrifolia) has been traditionally used in East Asia to treat diseases such as phlegm, cough, hangover, and fever. However, there is no investigation that evaluates the biological activities of the leaves of P. pyrifolia. This study aims at describing the anti-inflammatory effects of PP, a bioactive fraction from the leaves of P. pyrifolia, in lipopolysaccharide (LPS)-stimulated THP-1 cells. Initially, PP decreased the protein and RNA expression of TNF-α, MCP-1, IL-8, and IL-6 induced by LPS. Moreover, PP attenuated the phosphorylation of p38, JNK, and ERK. In addition, after stimulation with LPS, the degradation of IκB-α was suppressed by PP, and the phosphorylation of IκB-α and p65 was suppressed by PP. Additionally, PP increased HO-1, which controls the production of inflammatory molecules, by activating Nrf2. These results indicated that PP could be used as an anti-inflammatory drug to promote wellness.

show abstract

Differences in monocyte subsets are associated with short‐term survival in patients with septic shock

Abstract: This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Cited by 18 publications

References 42 publications

Development of Exhausted Memory Monocytes and Underlying Mechanisms

Development of Exhausted Memory Monocytes and Underlying Mechanisms

The Value of a Complete Blood Count (CBC) for Sepsis Diagnosis and Prognosis

Anti-Inflammatory Effects of the Fraction from the Leaves of Pyrus pyrifolia on LPS-Stimulated THP-1 Cells

Contact Info

Product

Resources

About