scholarly journals Gut Leakage of Fungal‐Related Products: Turning Up the Heat for HIV Infection

2021 ◽  
Vol 12 ◽  
Author(s):  
Stéphane Isnard ◽  
John Lin ◽  
Simeng Bu ◽  
Brandon Fombuena ◽  
Léna Royston ◽  
...  
Keyword(s):  
Hiv Infection ◽  
Immune Activation ◽  
Cell Function ◽  
Experimental Treatment ◽  
Intestinal Epithelial ◽  
Barrier Dysfunction ◽  
Gut Leakage ◽  
Microbial Products ◽  
Treatment Responses

The intestinal epithelial layer serves as a physical and functional barrier between the microbiota in the lumen and immunologically active submucosa. Th17 T-cell function protects the gut epithelium from aggression from microbes and their by-products. Loss of barrier function has been associated with enhanced translocation of microbial products which act as endotoxins, leading to local and systemic immune activation. Whereas the inflammatory role of LPS produced by Gram-negative bacteria has been extensively studied, the role of fungal products such as β-D-glucan remains only partially understood. As HIV infection is characterized by impaired gut Th17 function and increased gut permeability, we critically review mechanisms of immune activation related to fungal translocation in this viral infection. Additionally, we discuss markers of fungal translocation for diagnosis and monitoring of experimental treatment responses. Targeting gut barrier dysfunction and reducing fungal translocation are emerging strategies for the prevention and treatment of HIV-associated inflammation and may prove useful in other inflammatory chronic diseases.

scholarly journals The microbiome’s relationship with congenital heart disease: more than a gut feeling

2021 ◽  
Vol 5 (1) ◽  
Author(s):  
Dan Feng ◽  
Jason T. Christensen ◽  
Anji T. Yetman ◽  
Merry L. Lindsey ◽  
Amar B. Singh ◽  
...  
Keyword(s):  
Congenital Heart Disease ◽  
Heart Disease ◽  
Patient Population ◽  
Congenital Heart ◽  
Basic Research ◽  
Intestinal Epithelial ◽  
Barrier Dysfunction ◽  
Intestinal Dysbiosis ◽  
Epithelial Barrier Dysfunction

AbstractPatients with congenital heart disease (CHD) are at risk for developing intestinal dysbiosis and intestinal epithelial barrier dysfunction due to abnormal gut perfusion or hypoxemia in the context of low cardiac output or cyanosis. Intestinal dysbiosis may contribute to systemic inflammation thereby worsening clinical outcomes in this patient population. Despite significant advances in the management and survival of patients with CHD, morbidity remains significant and questions have arisen as to the role of the microbiome in the inflammatory process. Intestinal dysbiosis and barrier dysfunction experienced in this patient population are increasingly implicated in critical illness. This review highlights possible CHD-microbiome interactions, illustrates underlying signaling mechanisms, and discusses future directions and therapeutic translation of the basic research.

scholarly journals STAT3 Signalling via the IL-6ST/gp130 Cytokine Receptor Promotes Epithelial Integrity and Intestinal Barrier Function during DSS-Induced Colitis

Biomedicines ◽  
2021 ◽  
Vol 9 (2) ◽  
pp. 187
Author(s):  
Lokman Pang ◽  
Jennifer Huynh ◽  
Mariah G. Alorro ◽  
Xia Li ◽  
Matthias Ernst ◽  
...  
Keyword(s):  
Barrier Function ◽  
Intestinal Barrier ◽  
Intestinal Barrier Function ◽  
Intestinal Epithelial ◽  
Barrier Dysfunction ◽  
Epithelial Integrity ◽  
Barrier Integrity ◽  
Gp130 Receptor ◽  
Stat3 Signalling

The intestinal epithelium provides a barrier against commensal and pathogenic microorganisms. Barrier dysfunction promotes chronic inflammation, which can drive the pathogenesis of inflammatory bowel disease (IBD) and colorectal cancer (CRC). Although the Signal Transducer and Activator of Transcription-3 (STAT3) is overexpressed in both intestinal epithelial cells and immune cells in IBD patients, the role of the interleukin (IL)-6 family of cytokines through the shared IL-6ST/gp130 receptor and its associated STAT3 signalling in intestinal barrier integrity is unclear. We therefore investigated the role of STAT3 in retaining epithelial barrier integrity using dextran sulfate sodium (DSS)-induced colitis in two genetically modified mouse models, to either reduce STAT1/3 activation in response to IL-6 family cytokines with a truncated gp130∆STAT allele (GP130∆STAT/+), or by inducing short hairpin-mediated knockdown of Stat3 (shStat3). Here, we show that mice with reduced STAT3 activity are highly susceptible to DSS-induced colitis. Mechanistically, the IL-6/gp130/STAT3 signalling cascade orchestrates intestinal barrier function by modulating cytokine secretion and promoting epithelial integrity to maintain a defence against bacteria. Our study also identifies a crucial role of STAT3 in controlling intestinal permeability through tight junction proteins. Thus, therapeutically targeting the IL-6/gp130/STAT3 signalling axis to promote barrier function may serve as a treatment strategy for IBD patients.

scholarly journals ON THE QUESTION OF THE PATHOGENESIS OF HIV-INFECTION: THE ROLE OF IMMUNE ACTIVATION IN PROGRESSION OF DISEASE

2012 ◽  
Vol 17 (3) ◽  
pp. 47-52
Author(s):  
G. R. Khasanova ◽  
I. G. Mustafin ◽  
V. A. Anokhin
Keyword(s):  
Immune System ◽  
Gut Microbiota ◽  
Hiv Infection ◽  
Immune Activation ◽  
Opportunistic Pathogens ◽  
Rate Of Progression ◽  
Progression Of Disease ◽  
Modern Knowledge

Hyperactivaion of immme system is considered by most investigators as importantfactor, contributing to progression of HIV-infection and development ofAIDS. In the review modern knowledge about mechanisms and results of activation of immune system during HIV-infection are presented. HIV itself, opportunistic pathogens and components of gut microbiota, first of all, endotoxins ofgram-negative bacteria are considered as probable "activators" of immune system. High levels of endotoxin and markers of immune activation are associated with an even greater rate of progression of HIV-infection.

scholarly journals Immunovirological parameters and cytokines in HIV infection

2012 ◽  
Vol 45 (6) ◽  
pp. 663-669 ◽  
Author(s):  
Karen Ingrid Tasca ◽  
Sueli Aparecida Calvi ◽  
Lenice do Rosário de Souza
Keyword(s):  
Clinical Practice ◽  
Cardiovascular Diseases ◽  
Hiv Infection ◽  
Immune Activation ◽  
Healthy Individuals ◽  
Antiretroviral Therapies ◽  
The Many ◽  
Lower Morbidity

Although modern combined antiretroviral therapies (cART) result in lower morbidity and mortality and a visible improvement of clinical and laboratory parameters in HIV-infected, it is known that their long-term use contributes to appearance of the many events unrelated to AIDS such as cardiovascular diseases, cancer and osteoporosis, comorbidities which have been proposed as some of the most important that deprive the majority of infected to present an even better prognosis. This is because even with a decrease in inflammation and immune activation after drug intervention to the patient, these parameters remain higher than those shown by healthy individuals and the imbalance of cytokine profiles also persists. Therefore, evaluations of other biomarkers in clinical practice are needed to complement the exams already carried out routinely and allow more effective monitoring of HIV patients. This review aims to investigate the role of cytokines as potential markers showing studies on their behavior in various stages of HIV infection, with or without cART.

scholarly journals Pivotal role of M-DC8+ monocytes from viremic HIV-infected patients in TNFα overproduction in response to microbial products

Blood ◽  
2012 ◽  
Vol 120 (11) ◽  
pp. 2259-2268 ◽  
Author(s):  
Charles-Antoine Dutertre ◽  
Sonia Amraoui ◽  
Annalisa DeRosa ◽  
Jean-Pierre Jourdain ◽  
Lene Vimeux ◽  
...  
Keyword(s):  
Dendritic Cell ◽  
Hiv Infection ◽  
Mononuclear Cells ◽  
Inflammatory Diseases ◽  
Intestinal Epithelial ◽  
Color Flow ◽  
Gm Csf ◽  
Cell Counts

Abstract HIV infects activated CD4+ T cells and induces their depletion. Progressive HIV infection leading to AIDS is fueled by chronic immune hyperactivation, mediated by inflammatory cytokines like TNFα. This has been related to intestinal epithelial damage and microbial LPS translocation into the circulation. Using 11-color flow cytometry, cell sorting, and cell culture, we investigated the numbers and TNFα production of fully defined circulating dendritic cell and monocyte populations during HIV-1 infection. In 15 viremic, untreated patients, compared with 8 treated, virologically suppressed patients or to 13 healthy blood donors, circulating CD141 (BDCA-3)+ and CD1c (BDCA-1)+ dendritic cell counts were reduced. Conversely, CD14+CD16++ monocyte counts were increased, particularly those expressing M-DC8, while classical CD14++CD16−M-DC8− monocyte numbers were unchanged. Blood mononuclear cells from viremic patients produced more TNFα in response to LPS than those from virologically suppressed patients. M-DC8+ monocytes were mostly responsible for this overproduction. Moreover, M-DC8+ monocytes differentiated in vitro from classical monocytes using M-CSF and GM-CSF, which is increased in viremic patient's plasma. This M-DC8+ monocyte population, which is involved in the pathogenesis of chronic inflammatory diseases like Crohn disease, might thus be considered as a major actor in the immune hyperactivation fueling HIV infection progression.

scholarly journals Mucosal Th17 Cell Function Is Altered during HIV Infection and Is an Independent Predictor of Systemic Immune Activation

2013 ◽  
Vol 191 (5) ◽  
pp. 2164-2173 ◽  
Author(s):  
Connie J. Kim ◽  
Lyle R. McKinnon ◽  
Colin Kovacs ◽  
Gabor Kandel ◽  
Sanja Huibner ◽  
...  
Keyword(s):  
Hiv Infection ◽  
Immune Activation ◽  
Th17 Cell ◽  
Cell Function ◽  
Independent Predictor ◽  
Systemic Immune Activation

scholarly journals Role of STAT6 and Mast Cells in IL-4- and IL-13-Induced Alterations in Murine Intestinal Epithelial Cell Function

2002 ◽  
Vol 169 (8) ◽  
pp. 4417-4422 ◽  
Author(s):  
Kathleen B. Madden ◽  
Lucia Whitman ◽  
Carolyn Sullivan ◽  
William C. Gause ◽  
Joseph F. Urban ◽  
...  
Keyword(s):  
Mast Cells ◽  
Epithelial Cell ◽  
Intestinal Epithelial Cell ◽  
Cell Function ◽  
Intestinal Epithelial

scholarly journals CCAAT/Enhancer-Binding Protein Homologous Protein (CHOP) Deficiency Attenuates Heatstroke-Induced Intestinal Injury

Inflammation ◽  
2021 ◽  
Author(s):  
Yan Cao ◽  
Maiying Fan ◽  
Yanfang Pei ◽  
Lei Su ◽  
Weiwei Xiao ◽  
...  
Keyword(s):  
Protein Expression ◽  
Er Stress ◽  
Intestinal Barrier ◽  
Intestinal Injury ◽  
Intestinal Epithelial ◽  
Barrier Dysfunction ◽  
Homologous Protein

Abstract The intestine is one of the main target organs involved in the pathological process of heatstroke. CCAAT/enhancer-binding protein homologous protein (CHOP) is involved in endoplasmic reticulum (ER) stress-induced apoptosis. This study aimed to explore the role of CHOP in heatstroke-induced intestinal injury and potential therapy. An in vitro heat stress (HS) model using Caco-2 cells was employed. We observed the role of CHOP in apoptosis-mediated intestinal epithelial cell injury secondary to HS by evaluating cell viability, lactate dehydrogenase release, apoptosis levels, and GRP78, PERK, ATF4, CHOP, Bcl-2, and BAX mRNA and protein expression. To further study the role of CHOP in HS-induced intestinal barrier dysfunction, we assessed transepithelial electrical resistance, paracellular tracer flux, ultrastructure of tight junctions, and protein expression of ZO-1 and occludin. Male wild-type mice and CHOP knockout mice were used for in vivo experiments. We evaluated serum d-lactate and diamine oxidase levels, histopathological changes, intestinal ultrastructure, and ZO-1 and occludin protein expression. HS activated the PERK-CHOP pathway and promoted apoptosis by upregulating BAX and downregulating Bcl-2; these effects were prevented by CHOP silencing. Intestinal epithelial barrier function was disrupted by HS in vitro and in vivo. CHOP silencing prevented intestinal barrier dysfunction in Caco-2 cells, whereas CHOP knockout mice exhibited decreased intestinal mucosal injury. The ER stress inhibitor 4-phenylbutyrate (4-PBA) prevented HS-induced intestinal injury in vitro and in vivo. This study indicated that CHOP deficiency attenuates heatstroke-induced intestinal injury and may contribute to the identification of a novel therapy against heatstroke associated with the ER stress pathway.

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