scholarly journals Enteric immunity, the gut microbiome, and sepsis: Rethinking the germ theory of disease

2016 ◽  
Vol 242 (2) ◽  
pp. 127-139 ◽  
Author(s):  
Javier Cabrera-Perez ◽  
Vladimir P Badovinac ◽  
Thomas S Griffith
Keyword(s):  
Immune Responses ◽  
Systemic Inflammation ◽  
Gut Microbiome ◽  
Intestinal Flora ◽  
Medical Community ◽  
Microbial Populations ◽  
Special Focus ◽  
Adaptive Immune ◽  
Gut Epithelium ◽  
The Impact

Sepsis is a poorly understood syndrome of systemic inflammation responsible for hundreds of thousands of deaths every year. The integrity of the gut epithelium and competence of adaptive immune responses are notoriously compromised during sepsis, and the prevalent assumption in the scientific and medical community is that intestinal commensals have a detrimental role in the systemic inflammation and susceptibility to nosocomial infections seen in critically ill, septic patients. However, breakthroughs in the last decade provide strong credence to the idea that our mucosal microbiome plays an essential role in adaptive immunity, where a human host and its prokaryotic colonists seem to exist in a carefully negotiated armistice with compromises and benefits that go both ways. In this review, we re-examine the notion that intestinal contents are the driving force of critical illness. An overview of the interaction between the microbiome and the immune system is provided, with a special focus on the impact of commensals in priming and the careful balance between normal intestinal flora and pathogenic organisms residing in the gut microbiome. Based on the data in hand, we hypothesize that sepsis induces imbalances in microbial populations residing in the gut, along with compromises in epithelial integrity. As a result, normal antigen sampling becomes impaired, and proliferative cues are intermixed with inhibitory signals. This situates the microbiome, the gut, and its complex immune network of cells and bacteria, at the center of aberrant immune responses during and after sepsis.

scholarly journals SARS-CoV-2-Indigenous Microbiota Nexus: Does Gut Microbiota Contribute to Inflammation and Disease Severity in COVID-19?

2021 ◽  
Vol 11 ◽  
Author(s):  
Indranil Chattopadhyay ◽  
Esaki M. Shankar
Keyword(s):  
Gut Microbiota ◽  
Immune Responses ◽  
Gut Microbiome ◽  
Innate Immune ◽  
Innate Immune Responses ◽  
Targeted Interventions ◽  
Promising Therapeutic Approach ◽  
Indigenous Microbiota ◽  
The Impact ◽  
Microbiome Profiling

Gut microbiome alterations may play a paramount role in determining the clinical outcome of clinical COVID-19 with underlying comorbid conditions like T2D, cardiovascular disorders, obesity, etc. Research is warranted to manipulate the profile of gut microbiota in COVID-19 by employing combinatorial approaches such as the use of prebiotics, probiotics and symbiotics. Prediction of gut microbiome alterations in SARS-CoV-2 infection may likely permit the development of effective therapeutic strategies. Novel and targeted interventions by manipulating gut microbiota indeed represent a promising therapeutic approach against COVID-19 immunopathogenesis and associated co-morbidities. The impact of SARS-CoV-2 on host innate immune responses associated with gut microbiome profiling is likely to contribute to the development of key strategies for application and has seldom been attempted, especially in the context of symptomatic as well as asymptomatic COVID-19 disease.

scholarly journals Unity of bowel-lung axis and the role of beneficial microbiota in anti-infectious protection

2021 ◽  
Vol 4 (4) ◽  
pp. 355-361
Author(s):  
T.E. Taranushenko ◽  
Keyword(s):  
Immune Responses ◽  
Respiratory Infections ◽  
Human Microbiome ◽  
Human Microbiome Project ◽  
Medical Community ◽  
Mucosal Inflammation ◽  
Potential Interactions ◽  
The Impact ◽  
And Child Health

NIH Human Microbiome Project determined particular attention of the worldwide medical community to the study of the human microbiome and the assessment of the impact of symbiont microorganisms in the development of various (not only gastrointestinal) disorders. Potential interactions between the bowel and lungs (bowel-lung axis) via microbiota that allow for the possible involvement of microorganisms in the development of respiratory diseases are actively debated. This paper reviews studies on the pattern of interactions between bowel and lungs in infectious diseases associated with mucosal inflammation. The association between gut microbiota and the protective barrier of the respiratory tract based on known mechanisms and novel data derived from recent studies on SARS-CoV-2 is discussed. The relevance of beneficial bacteria (symbionts) in local and systemic immune responses, their disease-modifying and, eventually, therapeutic strategymodifying properties, the ability to be a resource of preventive medicine and an orchestrating tool for infections are addressed. Practitioners’ difficulties with probiotics in preventive and treatment schedules for various conditions are highlighted. Finally, the use of probiotics in children with respiratory infections and COVID-19 is uncovered. KEYWORDS: microbiota, microbiome, probiotics, children, mucosal immunity, Bifidobacterium. FOR CITATION: Taranushenko T.E. Unity of bowel-lung axis and the role of beneficial microbiota in anti-infectious protection. Russian Journal of Woman and Child Health. 2021;4(4):355–361 (in Russ.). DOI: 10.32364/2618-8430-2021-4-4-355-361.

scholarly journals Systemic inflammation in hemorrhagic strokes – A novel neurological sign and therapeutic target?

2019 ◽  
Vol 39 (6) ◽  
pp. 959-988 ◽  
Author(s):  
Aisha R Saand ◽  
Fang Yu ◽  
Jun Chen ◽  
Sherry H-Y Chou
Keyword(s):  
Brain Injury ◽  
Inflammatory Response ◽  
Immune Responses ◽  
Systemic Inflammation ◽  
Systemic Disease ◽  
Systemic Inflammatory Response ◽  
Organ Systems ◽  
Novel Therapeutic Strategies ◽  
The Impact ◽  
The Brain

Growing evidences suggest that stroke is a systemic disease affecting many organ systems beyond the brain. Stroke-related systemic inflammatory response and immune dysregulations may play an important role in brain injury, recovery, and stroke outcome. The two main phenomena in stroke-related peripheral immune dysregulations are systemic inflammation and post-stroke immunosuppression. There is emerging evidence suggesting that the spleen contracts following ischemic stroke, activates peripheral immune response and this may further potentiate brain injury. Whether similar brain–immune crosstalk occurs in hemorrhagic strokes such as intracerebral hemorrhage (ICH) and subarachnoid hemorrhage (SAH) is not established. In this review, we systematically examined animal and human evidence to date on peripheral immune responses associated with hemorrhagic strokes. Specifically, we reviewed the impact of clinical systemic inflammatory response syndrome (SIRS), inflammation- and immune-associated biomarkers, the brain–spleen interaction, and cellular mediators of peripheral immune responses to ICH and SAH including regulatory T cells (Tregs). While there is growing data suggesting that peripheral immune dysregulation following hemorrhagic strokes may be important in brain injury pathogenesis and outcome, details of this brain-immune system cross-talk remain insufficiently understood. This is an important unmet scientific need that may lead to novel therapeutic strategies in this highly morbid condition.

scholarly journals Anti-Telomerase CD4+ Th1 Immunity and Monocytic-Myeloid-Derived-Suppressor Cells Are Associated with Long-Term Efficacy Achieved by Docetaxel, Cisplatin, and 5-Fluorouracil (DCF) in Advanced Anal Squamous Cell Carcinoma: Translational Study of Epitopes-HPV01 and 02 Trials

2020 ◽  
Vol 21 (18) ◽  
pp. 6838 ◽  
Author(s):  
Laurie Spehner ◽  
Stefano Kim ◽  
Angélique Vienot ◽  
Eric François ◽  
Bruno Buecher ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
T Cells ◽  
Immune Responses ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Adaptive Immune Responses ◽  
Anal Squamous Cell Carcinoma ◽  
Adaptive Immune ◽  
Immunosuppressive Cells ◽  
The Impact

Docetaxel, cisplatin and 5-fluorouracil (DCF) chemotherapy regimen is highly effective in advanced anal squamous cell carcinoma (SCCA), as demonstrated by the Epitopes-HPV02 study results. Here, we analyzed the impact of DCF regimen and the prognostic value of adaptive immune responses and immunosuppressive cells in SCCA patients included in two prospective studies (Epitopes-HPV01 and HPV02). The presence of T-cell responses against Human papillomavirus (HPV)16-E6/E7 and anti-telomerase (hTERT)-antigens was measured by IFNᵧ-ELISpot. Here, we showed that HPV-adaptive immune responses are increased in SCCA patients. SCCA patients also displayed enhanced circulating TH1 T-cells restricted by hTERT. Exposition to DCF increased hTERT immunity but not HPV or common viruses immune responses. Notably, the correlation of hTERT immune responses with SCCA patients’ clinical outcomes highlights that hTERT is a relevant antigen in this HPV-related disease. The influence of peripheral immunosuppressive cells was investigated by flow cytometry. While both regulatory T-cells and monocytic-myeloid-derived suppressive cells (M-MDSC) accumulated in the peripheral blood of SCCA patients, only high levels of M-MDSC were negatively correlated with hTERT adaptive immune responses and predicted poor prognosis. Altogether, our results reveal that hTERT is a relevant antigen in HPV-driven SCCA disease and that M-MDSC levels influence TH1-adaptive immune responses and patients’ survival.

A MATHEMATICAL STUDY OF THE IMPLICIT ROLE OF INNATE AND ADAPTIVE IMMUNE RESPONSES ON WITHIN-HUMAN PLASMODIUM FALCIPARUM PARASITE LEVELS

2020 ◽  
Vol 28 (02) ◽  
pp. 377-429
Author(s):  
GIDEON A. NGWA ◽  
WOLDEGEBRIEL A. WOLDEGERIMA ◽  
MIRANDA I. TEBOH-EWUNGKEM
Keyword(s):  
Immune Responses ◽  
Parasite Development ◽  
Adaptive Immune Responses ◽  
Adaptive Immune ◽  
Plasmodium Falciparum Parasite ◽  
Number Formula ◽  
Parameter Measuring ◽  
System Variables ◽  
The Impact

A within-human-host malaria parasite model, integrating key variables that influence parasite evolution-progression-advancement, under innate and adaptive immune responses, is analyzed. The implicit role of immunity on the steady state parasite loads and parasitemia reproduction number ([Formula: see text]), a threshold parameter measuring the parasite’s annexing ability of healthy red blood cells (HRBCs), eventually rendering a human infectious to mosquitoes, is investigated. The impact of the type of recruitment function used to model HRBC growth is also investigated. The model steady states and [Formula: see text], both obtained as functions of immune system variables, are analyzed at snapshots of immune sizes. Model results indicate that the more the immune cells, innate and adaptive, the more efficient they are at inhibiting parasite development and progression; consequently, the less severe the malaria disease in a patient. Our analysis also illustrates the existence of a Hopf bifurcation leading to a limit cycle, observable only for the nonlinear recruitment functions, at reasonably large [Formula: see text].

scholarly journals The immunology of Zika Virus

F1000Research ◽  
2018 ◽  
Vol 7 ◽  
pp. 203 ◽  
Author(s):  
Abigail Culshaw ◽  
Juthathip Mongkolsapaya ◽  
Gavin Screaton
Keyword(s):  
Immune Responses ◽  
Zika Virus ◽  
Effective Vaccine ◽  
Comprehensive Understanding ◽  
Adaptive Immune Responses ◽  
Zikv Infection ◽  
Virus Identification ◽  
Adaptive Immune ◽  
Poor Outcomes ◽  
The Impact

Zika virus (ZIKV) was initially thought to cause only mild, self-limiting symptoms. However, recent outbreaks have been associated with the autoimmune disease Guillain-Barré syndrome and causally linked to a congenital malformation known as microcephaly. This has led to an urgent need for a safe and effective vaccine. A comprehensive understanding of the immunology of ZIKV infection is required to aid in the design of such a vaccine. Whilst details of both innate and adaptive immune responses to ZIKV are emerging, further research is needed. As immunopathogenesis has been implicated in poor outcomes following infection with the related dengue virus, identification of cross-reactive immune responses between flaviviruses and the impact they may have on disease progression is also of high importance.

scholarly journals CpG in Combination with an Inhibitor of Notch Signaling Suppresses Formalin-Inactivated Respiratory Syncytial Virus-Enhanced Airway Hyperresponsiveness and Inflammation by Inhibiting Th17 Memory Responses and Promoting Tissue-Resident Memory Cells in Lungs

2017 ◽  
Vol 91 (10) ◽  
Author(s):  
Lei Zhang ◽  
Hongyong Li ◽  
Yan Hai ◽  
Wei Yin ◽  
Wenjian Li ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
Immune Responses ◽  
Notch Signaling ◽  
Airway Inflammation ◽  
Airway Hyperresponsiveness ◽  
Adaptive Immune Responses ◽  
Tlr Signaling ◽  
Adaptive Immune ◽  
Syncytial Virus ◽  
The Impact

ABSTRACT Respiratory syncytial virus (RSV) is the leading cause of childhood hospitalizations. The formalin-inactivated RSV (FI-RSV) vaccine-enhanced respiratory disease (ERD) has been an obstacle to the development of a safe and effective killed RSV vaccine. Agonists of Toll-like receptor (TLR) have been shown to regulate immune responses induced by FI-RSV. Notch signaling plays critical roles during the differentiation and effector function phases of innate and adaptive immune responses. Cross talk between TLR and Notch signaling pathways results in fine-tuning of TLR-triggered innate inflammatory responses. We evaluated the impact of TLR and Notch signaling on ERD in a murine model by administering CpG, an agonist of TLR9, in combination with L685,458, an inhibitor of Notch signaling during FI-RSV immunization. Activation with CpG or deficiency of MyD88-dependent TLR signaling did not alleviate airway inflammation in FI-RSV-immunized mice. Activation or inhibition of Notch signaling with Dll4, one of the Notch ligands, or L685,458 did not suppress FI-RSV-enhanced airway inflammation either. However, the CpG together with L685,458 markedly inhibited FI-RSV-enhanced airway hyperresponsiveness, weight loss, and lung inflammation. Interestingly, CpG plus L685,458 completely inhibited FI-RSV-associated Th17 and Th17-associated proinflammatory chemokine responses in lungs following RSV challenge but not Th1 or Th2, memory responses. In addition, FI-RSV plus CpG plus L685,458 promoted protective CD8+ lung tissue-resident memory (TRM) cells. These results indicate that activation of TLR signaling combined with inhibition of Notch signaling prevent FI-RSV ERD, and the mechanism appears to involve suppressing proinflammatory Th17 memory responses and promoting protective TRM in lungs. IMPORTANCE RSV is the most important cause of lower respiratory tract infections in infants. The FI-RSV-enhanced respiratory disease (ERD) is a major impediment to the development of a safe and effective killed RSV vaccine. Using adjuvants to regulate innate and adaptive immune responses could be an effective method to prevent ERD. We evaluated the impact of TLR and Notch signaling on ERD by administering CpG, an agonist of TLR9, in combination with L685,458, an inhibitor of Notch signaling, during FI-RSV immunization. The data showed that treatment of TLR or Notch signaling alone did not suppress FI-RSV-enhanced airway inflammation, while CpG plus L685,458 markedly inhibited ERD. The mechanism appears to involve suppressing Th17 memory responses and promoting tissue-resident memory cells. Moreover, these results suggest that regulation of lung immune memory with adjuvant compounds containing more than one immune-stimulatory molecule may be a good strategy to prevent FI-RSV ERD.

scholarly journals Influenza Virus and Vaccination

Pathogens ◽  
2020 ◽  
Vol 9 (3) ◽  
pp. 220
Author(s):  
Aitor Nogales ◽  
Marta L. DeDiego
Keyword(s):  
Influenza Virus ◽  
Immune Responses ◽  
Respiratory Disease ◽  
Public Health Problem ◽  
Special Focus ◽  
Virus Infections ◽  
Special Issue ◽  
Factors Associated ◽  
Adaptive Immune ◽  
Substantial Morbidity

Influenza virus infections represent a serious public health problem causing contagious respiratory disease and substantial morbidity and mortality in humans, resulting in a considerable economic burden worldwide. Notably, the number of deaths due to influenza exceeds that of any other known pathogen. Moreover, influenza infections can differ in their intensity, from mild respiratory disease to pneumonia, which can lead to death. Articles in this Special Issue have addressed different aspects of influenza in human health, and the advances in influenza research leading to the development of better therapeutics and vaccination strategies, with a special focus on the study of factors associated with innate or adaptive immune responses to influenza vaccination and/or infection.

scholarly journals The Impact of the Myeloid Response to Radiation Therapy

2013 ◽  
Vol 2013 ◽  
pp. 1-14 ◽  
Author(s):  
Michael J. Gough ◽  
Kristina Young ◽  
Marka Crittenden
Keyword(s):  
Radiation Therapy ◽  
Immune Responses ◽  
Adaptive Immunity ◽  
Residual Cancer ◽  
Effector Cells ◽  
Adaptive Immune ◽  
Treatment Site ◽  
Inflammatory Damage ◽  
Cancer Models ◽  
The Impact

Radiation therapy is showing potential as a partner for immunotherapies in preclinical cancer models and early clinical studies. As has been discussed elsewhere, radiation provides debulking, antigen and adjuvant release, and inflammatory targeting of effector cells to the treatment site, thereby assisting multiple critical checkpoints in antitumor adaptive immunity. Adaptive immunity is terminated by inflammatory resolution, an active process which ensures that inflammatory damage is repaired and tissue function is restored. We discuss how radiation therapy similarly triggers inflammation followed by repair, the consequences to adaptive immune responses in the treatment site, and how the myeloid response to radiation may impact immunotherapies designed to improve control of residual cancer cells.

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