Perinatal Environment Shapes Microbiota Colonization And Infant Growth: Impact On Host Response And Intestinal Function

Abstract Background Early microbial colonization triggers processes that result in intestinal maturation and immune priming. Perinatal factors, especially those associated with birth, including both mode and place of delivery are critical to shaping the infant gut microbiota with potential health consequences. Methods Gut microbiota profile of 180 healthy infants (n=23 born at home and n=157 born in hospital, 41.7% via caesarean section [CS]) was analyzed by 16S rRNA gene sequencing at birth, seven days and one month of life. Breastfeeding habits, infant clinical data, including length, weight and antibiotic exposure, were collected up to 18 months of life. Long-term personalized in vitro models of the intestinal epithelium and innate immune system were used to assess the link between gut microbiota composition, intestinal function and immune response. Results Microbiota profiles were shaped by the place and mode of delivery, and they had a distinct biological impact on the immune response and intestinal function in epithelial/immune cell models. Bacteroidetes and Bifidobacterium genus were decreased in C-section infants, who showed higher z-scores BMI and W/L during the first 18 months of life. Intestinal simulated epithelium had a stronger epithelial barrier function and intestinal maturation, alongside a higher immunological response (TLR4 route activation and pro-inflammatory cytokine release), when exposed to home-birth fecal supernatants, compared with CS. Distinct host response could be associated with different microbiota profiles. Conclusions Mode and place of birth influence the neonatal gut microbiota, likely shaping its interplay with the host through the maturation of the intestinal epithelium, regulation of the intestinal epithelial barrier and control of the innate immune system during early life, which can affect the phenotypic responses linked to metabolic processes in infants.

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Perinatal Environment Shapes Microbiota Colonization And Infant Growth: Impact On Host Response And Intestinal Function

10.21203/rs.3.rs-20279/v2 ◽

2020 ◽

Author(s):

Maria Carmen Collado ◽

Marta Selma-Royo ◽

Marta Calatayud ◽

Izaskun García-Mantrana ◽

Anna Parra-Llorca ◽

...

Keyword(s):

Immune Response ◽

Immune System ◽

Gut Microbiota ◽

Intestinal Epithelium ◽

Innate Immune System ◽

Host Response ◽

Innate Immune ◽

Epithelial Barrier ◽

Intestinal Function ◽

Intestinal Maturation

Abstract Background: Early microbial colonization triggers processes that result in intestinal maturation and immune priming. Perinatal factors, especially those associated with birth, including both mode and place of delivery are critical to shaping the infant gut microbiota with potential health consequences. Methods: Gut microbiota profile of 180 healthy infants (n=23 born at home and n=157 born in hospital, 41.7% via caesarean section [CS]) was analyzed by 16S rRNA gene sequencing at birth, seven days and one month of life. Breastfeeding habits, infant clinical data, including length, weight and antibiotic exposure, were collected up to 18 months of life. Long-term personalized in vitro models of the intestinal epithelium and innate immune system were used to assess the link between gut microbiota composition, intestinal function and immune response. Results: Microbiota profiles were shaped by the place and mode of delivery, and they had a distinct biological impact on the immune response and intestinal function in epithelial/immune cell models. Bacteroidetes and Bifidobacterium genus were decreased in C-section infants, who showed higher z-scores BMI and W/L during the first 18 months of life. Intestinal simulated epithelium had a stronger epithelial barrier function and intestinal maturation, alongside a higher immunological response (TLR4 route activation and pro-inflammatory cytokine release), when exposed to home-birth fecal supernatants, compared with CS. Distinct host response could be associated with different microbiota profiles. Conclusions: Mode and place of birth influence the neonatal gut microbiota, likely shaping its interplay with the host through the maturation of the intestinal epithelium, regulation of the intestinal epithelial barrier and control of the innate immune system during early life, which can affect the phenotypic responses linked to metabolic processes in infants.

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Perinatal environment shapes microbiota colonization and infant growth: impact on host response and intestinal function

Microbiome ◽

10.1186/s40168-020-00940-8 ◽

2020 ◽

Vol 8 (1) ◽

Author(s):

M. Selma-Royo ◽

M. Calatayud Arroyo ◽

I. García-Mantrana ◽

A. Parra-Llorca ◽

R. Escuriet ◽

...

Keyword(s):

Immune Response ◽

Immune System ◽

Gut Microbiota ◽

Intestinal Epithelium ◽

Innate Immune System ◽

Host Response ◽

Innate Immune ◽

Epithelial Barrier ◽

Intestinal Function ◽

Intestinal Maturation

Abstract Background Early microbial colonization triggers processes that result in intestinal maturation and immune priming. Perinatal factors, especially those associated with birth, including both mode and place of delivery are critical to shaping the infant gut microbiota with potential health consequences. Methods Gut microbiota profile of 180 healthy infants (n = 23 born at home and n = 157 born in hospital, 41.7% via cesarean section [CS]) was analyzed by 16S rRNA gene sequencing at birth, 7 days, and 1 month of life. Breastfeeding habits and infant clinical data, including length, weight, and antibiotic exposure, were collected up to 18 months of life. Long-term personalized in vitro models of the intestinal epithelium and innate immune system were used to assess the link between gut microbiota composition, intestinal function, and immune response. Results Microbiota profiles were shaped by the place and mode of delivery, and they had a distinct biological impact on the immune response and intestinal function in epithelial/immune cell models. Bacteroidetes and Bifidobacterium genus were decreased in C-section infants, who showed higher z-scores BMI and W/L during the first 18 months of life. Intestinal simulated epithelium had a stronger epithelial barrier function and intestinal maturation, alongside a higher immunological response (TLR4 route activation and pro-inflammatory cytokine release), when exposed to home-birth fecal supernatants, compared with CS. Distinct host response could be associated with different microbiota profiles. Conclusions Mode and place of birth influence the neonatal gut microbiota, likely shaping its interplay with the host through the maturation of the intestinal epithelium, regulation of the intestinal epithelial barrier, and control of the innate immune system during early life, which can affect the phenotypic responses linked to metabolic processes in infants. Trial registration NCT03552939.

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Insights into Sensing of Murine Retroviruses

Viruses ◽

10.3390/v12080836 ◽

2020 ◽

Vol 12 (8) ◽

pp. 836

Author(s):

Eileen A. Moran ◽

Susan R. Ross

Keyword(s):

Immune Response ◽

Immune System ◽

Nucleic Acid ◽

Adaptive Immunity ◽

Innate Immune System ◽

Innate Immune ◽

Genetic Tool ◽

Causes Of Disease ◽

Retrovirus Infection ◽

Insight Into

Retroviruses are major causes of disease in animals and human. Better understanding of the initial host immune response to these viruses could provide insight into how to limit infection. Mouse retroviruses that are endemic in their hosts provide an important genetic tool to dissect the different arms of the innate immune system that recognize retroviruses as foreign. Here, we review what is known about the major branches of the innate immune system that respond to mouse retrovirus infection, Toll-like receptors and nucleic acid sensors, and discuss the importance of these responses in activating adaptive immunity and controlling infection.

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Phenoloxidase activity and haemolymph cytology in honeybees challenged with a virus suspension (deformed wings virus DWV) or phosphate buffered suspension (PBS)

Ciência Rural ◽

10.1590/0103-8478cr20180726 ◽

2019 ◽

Vol 49 (2) ◽

Cited By ~ 3

Author(s):

Francesca Millanta ◽

Simona Sagona ◽

Maurizio Mazzei ◽

Mario Forzan ◽

Alessandro Poli ◽

...

Keyword(s):

Immune Response ◽

Immune System ◽

Immune Responses ◽

Innate Immune System ◽

Innate Immune ◽

Additional Stress ◽

Varroa Mite ◽

Virus Suspension ◽

Phenoloxidase Activity ◽

Cell Immunity

ABSTRACT: The innate immune system of honeybees mainly consists in antimicrobial peptides, cellular immunity and melanisation. In order to investigate the immune response of honeybees to immune stressors, three stress degrees were tested. Newly emerged bees naturally DWV-infected were collected from a Varroa mite-free apiary and divided into three experimental groups: naturally DWV infected bees, PBS injected bees, and artificially DWV super infected bees. Phenoloxidase activity and haemolymph cellular subtype count were investigated. Phenoloxidase activity was highest (P<0.05) in DWV-superinfected bees, and the haemocyte population differed within the three observed groups. Although, immune responses following DWV infection have still not been completely clarified, this investigation sheds light on the relation between cell immunity and the phenoloxidase activity of DWV-naturally infected honeybees exposed to additional stress such as injury and viral superinfection.

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P53 and The Immune Response: 40 Years of Exploration—A Plan for the Future

International Journal of Molecular Sciences ◽

10.3390/ijms21020541 ◽

2020 ◽

Vol 21 (2) ◽

pp. 541 ◽

Cited By ~ 11

Author(s):

Arnold J. Levine

Keyword(s):

Immune Response ◽

Immune System ◽

Innate Immune System ◽

P53 Protein ◽

P53 Gene ◽

T Cell Response ◽

Innate Immune ◽

Transplantation Antigen ◽

Mutant Form ◽

The Future

The p53 field was born from a marriage of the techniques of cancer virus research and immunology. Over the past 40 years, it has followed the path of cancer research. Now cancer treatments are turning to immunotherapy, and there are many hints of the role of the p53 protein in both the regulation of the innate immune system and as an antigen in adaptive immune responses. The p53 gene and protein are part of the innate immune system, and play an important role in infectious diseases, senescence, aging, and the surveillance of repetitive DNA and RNAs. The mutant form of the p53 protein in cancers elicits both a B-cell antibody response (a tumor antigen) and a CD-8 killer T-cell response (a tumor-specific transplantation antigen). The future will take the p53-immune response field of research into cancer immunotherapy, autoimmunity, inflammatory responses, neuro-degeneration, aging, and life span, and the regulation of epigenetic stability and tissue regeneration. The next 40 years will bring the p53 gene and its proteins out of a cancer focus and into an organismic and environmental focus.

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Insights into Innate Immune Response Against SARS-CoV-2 Infection

Revista Romana de Medicina de Laborator ◽

10.2478/rrlm-2021-0022 ◽

2021 ◽

Vol 29 (3) ◽

pp. 255-269

Author(s):

Adina Huțanu ◽

Anca Meda Georgescu ◽

Akos Vince Andrejkovits ◽

William Au ◽

Minodora Dobreanu

Keyword(s):

Immune Response ◽

Immune System ◽

Innate Immune Response ◽

Innate Immune System ◽

Time Course ◽

Adaptive Immune Response ◽

Innate Immune ◽

Interferon Response ◽

Humoral Factors ◽

Key Steps

Abstract The innate immune system is mandatory for the activation of antiviral host defense and eradication of the infection. In this regard, dendritic cells, natural killer cells, macrophages, neutrophils representing the cellular component, and cytokines, interferons, complement or Toll-Like Receptors, representing the mediators of unspecific response act together for both activation of the adaptive immune response and viral clearance. Of great importance is the proper functioning of the innate immune response from the very beginning. For instance, in the early stages of viral infection, the defective interferon response leads to uncontrolled viral replication and pathogen evasion, while hypersecretion during the later stages of infection generates hyperinflammation. This cascade activation of systemic inflammation culminates with cytokine storm syndrome and hypercoagulability state, due to a close interconnection between them. Thus an unbalanced reaction, either under- or over- stimulation of the innate immune system will lead to an uncoordinated response and unfavorable disease outcomes. Since both cellular and humoral factors are involved in the time-course of the innate immune response, in this review we aimed to address their gradual involvement in the antiviral response with emphasis on key steps in SARS-CoV-2 infection.

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SARS-CoV-2 and interferon blockade

Molecular Medicine ◽

10.1186/s10020-020-00231-w ◽

2020 ◽

Vol 26 (1) ◽

Author(s):

Betty Diamond ◽

Bruce T. Volpe ◽

Sonya VanPatten ◽

Yousef Al Abed

Keyword(s):

Immune Response ◽

Immune System ◽

Innate Immune System ◽

Neutralizing Antibodies ◽

Cytotoxic T Cells ◽

Adaptive Immune Response ◽

Innate Immune ◽

Interferon Production ◽

Therapeutic Implications ◽

Adaptive Immune

Abstract The response to viral infection generally includes an activation of the adaptive immune response to produce cytotoxic T cells and neutralizing antibodies. We propose that SARS-CoV-2 activates the innate immune system through the renin-angiotensin and kallikrein-bradykinin pathways, blocks interferon production and reduces an effective adaptive immune response. This model has therapeutic implications.

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Orchestration of Adaptive T Cell Responses by Neutrophil Granule Contents

Mediators of Inflammation ◽

10.1155/2019/8968943 ◽

2019 ◽

Vol 2019 ◽

pp. 1-15 ◽

Cited By ~ 6

Author(s):

Danielle Minns ◽

Katie Jane Smith ◽

Emily Gwyer Findlay

Keyword(s):

Immune Response ◽

Immune System ◽

T Cell ◽

Innate Immune System ◽

Adaptive Immune Response ◽

Innate Immune ◽

T Cell Immunity ◽

Cell Responses ◽

Adaptive Immune ◽

Cell Immunity

Neutrophils are the most abundant leukocytes in peripheral blood and respond rapidly to danger, infiltrating tissues within minutes of infectious or sterile injury. Neutrophils were long thought of as simple killers, but now we recognise them as responsive cells able to adapt to inflammation and orchestrate subsequent events with some sophistication. Here, we discuss how these rapid responders release mediators which influence later adaptive T cell immunity through influences on DC priming and directly on the T cells themselves. We consider how the release of granule contents by neutrophils—through NETosis or degranulation—is one way in which the innate immune system directs the phenotype of the adaptive immune response.

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A Novel View of Human Helicobacter pylori Infections: Interplay between Microbiota and Beta-Defensins

Biomolecules ◽

10.3390/biom9060237 ◽

2019 ◽

Vol 9 (6) ◽

pp. 237 ◽

Cited By ~ 15

Author(s):

Pero ◽

Brancaccio ◽

Laneri ◽

Biasi ◽

Lombardo ◽

...

Keyword(s):

Helicobacter Pylori ◽

Immune System ◽

Gut Microbiota ◽

Host Response ◽

Pathogenic Bacteria ◽

Precancerous Lesions ◽

Innate Immune ◽

Microbial Infections ◽

Beta Defensins ◽

The Impact

The gut microbiota is significantly involved in the preservation of the immune system of the host, protecting it against the pathogenic bacteria of the stomach. The correlation between gut microbiota and the host response supports human gastric homeostasis. Gut microbes may be shifted in Helicobacter pylori (Hp)-infected individuals to advance gastric inflammation and distinguished diseases. Particularly interesting is the establishment of cooperation between gut microbiota and antimicrobial peptides (AMPs) of the host in the gastrointestinal tract. AMPs have great importance in the innate immune reactions to Hp and participate in conservative co-evolution with an intricate microbiome. β-Defensins, a class of short, cationic, arginine-rich proteins belonging to the AMP group, are produced by epithelial and immunological cells. Their expression is enhanced during Hp infection. In this review, we discuss the impact of the gut microbiome on the host response, with particular regard to β-defensins in Hp-associated infections. In microbial infections, mostly in precancerous lesions induced by Hp infection, these modifications could lead to different outcomes.

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Basic Immunology

Tutorial Topics in Infection for the Combined Infection Training Programme ◽

10.1093/oso/9780198801740.003.0012 ◽

2019 ◽

Author(s):

Jonathan Lambourne ◽

Ruaridh Buchanan

Keyword(s):

Immune Response ◽

Immune System ◽

Epithelial Cells ◽

Immune Cells ◽

Innate Immune System ◽

Adaptive Immune System ◽

Lymphoid Organs ◽

Innate Immune ◽

Adaptive Immune ◽

Pathogen Entry

There are four major components of the immune system. These include: 1. mechanical barriers to pathogen entry. 2. the innate immune system. 3. the adaptive immune system. 4. the lymphoid organs. Mechanical barriers include skin and mucous membranes and tight junctions between epithelial cells prevent pathogen entry. Breaches can be iatrogenic, for example, IV lines, surgical wounds, and mucositis, and are a large source of healthcare- associated infections. The innate immune system provides the first internal line of defence, as well as initiating and shaping the adaptive immune response. The innate system comprises a range of responses: phagocytosis by neutrophils and macrophages (guided in part by the adaptive immune system), the complement cascade, and the release of antimicrobial peptides by epithelial cells (e.g. defensins, cathelicidin). The adaptive immune system includes both humoral (antibody- mediated) and cell-mediated responses. It is capable of greater diversity and specificity than the innate immune system, and can develop memory to pathogens and provide increased protection on re-exposure. Immune cells are divided into myeloid cells (neutrophils, eosinophils, basophils, mast cells, and monocytes/macrophages) and lymphoid cells (B, T, and NK cells). These all originate in the bone marrow from pluripotent haematopoietic stem cells. The lymphoid organs include the spleen, the lymph nodes, and mucosal-associated lymphoid tissues—which respond to antigens in the blood, tissues, and epithelial surfaces respectively. The three main ‘professional’ phagocytes are macrophages, dendritic cells, and neutrophils. They are similar with respect to how they recognize pathogens, but differ in their principal location and effector functions. Phagocytes express an array of Pattern Recognition Receptors (PRRs) e.g. Toll-like receptors and lectins (proteins that bind carbohydrates). PRRs recognize Pathogen- Associated Molecular Patterns (PAMPs)— elements which are conserved across species, such as cell-surface glycoproteins and nucleic acid sequences. Though limited in number, PRRs have evolved to recognize a huge array of pathogens. Binding of PRRs to PAMPs enhances phagocytosis. Macrophages are tissue-resident phagocytes, initiating and co-ordinating the local immune response. The cytokines and chemokines they produce cause vasodilation and alter the expression of endothelial cell adhesion factors, recruiting circulating immune cells.

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