Comparison of intestinal APC subsets from homeostatic and immunostimulatory environments

Naive T Cells ◽

Naïve T Cells ◽

Adaptive Immune ◽

Inflammatory Bowel

<p>Antigen presenting cells (APC) including dendritic cells (DC) play a key role in the initiation and direction of adaptive immune responses. Acting as sentinels in the tissue, DC sample antigen and traffic to the local lymph node where they present antigen to naïve T cells. The signals DC provide to naïve T cells determines the functional fate of the T cell and therefore, the type of immune response generated. At mucosal sites, such as the intestine, immune responses need to be carefully regulated due to the high antigenic load. For this reason, intestinal immune cells are highly specialised to prevent immune activation to innocuous antigens while still holding the capacity to induce potent responses to pathogenic microbes and helminths. Oral administration of antigen is associated with tolerance and the generation of FoxP3+ regulatory T cells (Tregs). Specialised lamina propria (LP) resident APC are required for the initiation of Treg differentiation in the mesenteric lymph nodes (MLN) through production of chemical mediators such as retinoic acid (RA). Ablation of these populations or restricted trafficking prevents the development of Tregs in mouse models thus supporting the essential role of APC in maintaining intestinal homeostasis. During infection, APC promote the induction of adaptive immune responses which neutralise threats. However, the APC subsets involved in this are not well defined. Pathologies such as food allergy and inflammatory bowel disease are thought to arise due to the development of aberrant immune responses. Food allergy can be modelled in mice using the mucosal adjuvant cholera toxin (CT) which has been shown to drive immunity to co-delivered antigens and is associated with the generation of IL-4 producing T helper 2 cells. Understanding the APC subsets involved in the initiation of intestinal immune responses could help in the development of targeted therapies for inflammatory bowel conditions. In this thesis, I show that oral administration of CT is followed by the appearance of a novel phenotype of DC in the intestinal LP and MLN. These DC differ functionally from DC at steady-state and may contribute to the generation of IL-4 producing T cells observed in the LP, MLN and spleen following oral administration of CT.</p>

Comparison of intestinal APC subsets from homeostatic and immunostimulatory environments

10.26686/wgtn.17007781.v1 ◽

2021 ◽

Author(s):

◽

Kerry Hilligan

Keyword(s):

T Cells ◽

Food Allergy ◽

Immune Responses ◽

Oral Administration ◽

Mesenteric Lymph Nodes ◽

Naive T Cells ◽

Naïve T Cells ◽

Adaptive Immune ◽

Inflammatory Bowel

Faculty Opinions recommendation of T cell memory. Resident memory CD8 T cells trigger protective innate and adaptive immune responses.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.718549286.793500135 ◽

2014 ◽

Author(s):

Torben Lund

Keyword(s):

T Cells ◽

T Cell ◽

Immune Responses ◽

Cd8 T Cells ◽

T Cell Memory ◽

Cell Memory ◽

Memory Cd8 T Cells ◽

Lactiplantibacillus plantarum as a Potential Adjuvant and Delivery System for the Development of SARS-CoV-2 Oral Vaccines

Microorganisms ◽

10.3390/microorganisms9040683 ◽

2021 ◽

Vol 9 (4) ◽

pp. 683

Author(s):

Julio Villena ◽

Chang Li ◽

Maria Guadalupe Vizoso-Pinto ◽

Jacinto Sacur ◽

Linzhu Ren ◽

...

Keyword(s):

Immune Responses ◽

Oral Administration ◽

Molecular Mechanisms ◽

Spike Protein ◽

Heterologous Proteins ◽

Oral Vaccines ◽

Adaptive Immune ◽

Viral Antigens ◽

Mucosal Infection

The most important characteristics regarding the mucosal infection and immune responses against the Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) as well as the current vaccines against coronavirus disease 2019 (COVID-19) in development or use are revised to emphasize the opportunity for lactic acid bacteria (LAB)-based vaccines to offer a valid alternative in the fight against this disease. In addition, this article revises the knowledge on: (a) the cellular and molecular mechanisms involved in the improvement of mucosal antiviral defenses by beneficial Lactiplantibacillus plantarum strains, (b) the systems for the expression of heterologous proteins in L. plantarum and (c) the successful expressions of viral antigens in L. plantarum that were capable of inducing protective immune responses in the gut and the respiratory tract after their oral administration. The ability of L. plantarum to express viral antigens, including the spike protein of SARS-CoV-2 and its capacity to differentially modulate the innate and adaptive immune responses in both the intestinal and respiratory mucosa after its oral administration, indicates the potential of this LAB to be used in the development of a mucosal COVID-19 vaccine.

Healthy Effects Exerted by Prebiotics, Probiotics, and Symbiotics with Special Reference to their Impact on the Immune System

International Journal for Vitamin and Nutrition Research ◽

10.1024/0300-9831/a000112 ◽

2012 ◽

Vol 82 (3) ◽

pp. 200-208 ◽

Cited By ~ 23

Author(s):

Emilio Jirillo ◽

Felicita Jirillo ◽

Thea Magrone

Keyword(s):

Immune Responses ◽

Tumor Development ◽

The Elderly ◽

Free Living ◽

Beneficial Effects ◽

Adaptive Immune ◽

Inflammatory Conditions ◽

Reduced Frequency ◽

Inflammatory Bowel

Pre-, pro-, and symbiotics are endowed with a broad spectrum of beneficial effects when administered to animals and humans. A series of experimental and clinical studies have clearly demonstrated that prebiotics, probiotics, or their combination are very effective in attenuating chronic inflammatory conditions such as inflammatory bowel disease or obesity. In addition, these natural products are able to prevent or arrest tumor development, acting on the intestinal microbiota as well as potentiating the immune response.Aging is characterized by a dramatic reduction of both innate and adaptive immune responses, the so-called immunosenescence. This leads to an increased incidence of infections, autoimmune diseases, and cancer in the elderly. Pre-, pro-, and symbiotic administration has been shown to ameliorate the immune response in aging. In particular, administration of a symbiotic to free-living elderly was able to potentiate the release of interleukin-8, thus increasing neutrophils in the host, perhaps explaining the reduced frequency of winter infections in the elderly.

Efficient migration of dendritic cells toward lymph node chemokines and induction of TH1 responses require maturation stimulus and apoptotic cell interaction

Blood ◽

10.1182/blood-2004-10-3991 ◽

2005 ◽

Vol 106 (5) ◽

pp. 1734-1741 ◽

Cited By ~ 26

Author(s):

Nicolas Bertho ◽

Henri Adamski ◽

Louis Toujas ◽

Martine Debove ◽

Jean Davoust ◽

...

Keyword(s):

T Cells ◽

Dendritic Cells ◽

Lymph Node ◽

Immune Responses ◽

Tumor Cells ◽

Apoptotic Cell ◽

Apoptotic Cells ◽

Naive T Cells ◽

Naïve T Cells ◽

Tnf Α

Abstract Dendritic cells (DCs) have the unique ability to initiate primary immune responses, and they can be conditioned for vaccinal purposes to present antigens after the engulfment of apoptotic cells. To recruit the rare antigen-specific naive T cells, DCs require a maturation step and subsequent transport toward lymph node (LN). To date, prostaglandin E2 (PGE2) is the best-characterized compound inducing this LN-directed migration in vitro, but PGE2 may skew the immune responses in a TH2 direction. We demonstrate here that on incubation with apoptotic tumor cells and tumor necrosis factor-α (TNF-α) or lipopolysaccharide (LPS), human monocyte-derived DCs become fully mature and acquire high migratory capacities toward LN-directing chemokines. The migration of TNF-α-treated DCs occurs only after cotreatment with apoptotic cells but not with necrotic cells. DC migration requires CD36 expression and incubation with apoptotic cells in the presence of heat-labile serum components. Moreover, on treatment with apoptotic cells and LPS, the migrating DCs are able to recruit naive T cells to generate TH1 immune responses. Our results show that the cotreatment of DCs with apoptotic tumor cells and inflammatory signals is promising for the design of an antitumoral DC-based vaccine. (Blood. 2005;106:1734-1741)

A Comprehensive Review and Update on the Pathogenesis of Inflammatory Bowel Disease

Journal of Immunology Research ◽

10.1155/2019/7247238 ◽

2019 ◽

Vol 2019 ◽

pp. 1-16 ◽

Cited By ~ 35

Author(s):

Qingdong Guan

Keyword(s):

Inflammatory Bowel Disease ◽

Immune Responses ◽

Bowel Disease ◽

Genetic Factors ◽

Intestinal Inflammation ◽

Adaptive Immune ◽

Host Genetic ◽

Inflammatory Bowel ◽

Host Genetic Factors

Inflammatory bowel disease (IBD) is a chronic and life-threating inflammatory disease of gastroenteric tissue characterized by episodes of intestinal inflammation. The pathogenesis of IBD is complex. Recent studies have greatly improved our knowledge of the pathophysiology of IBD, leading to great advances in the treatment as well as diagnosis of IBD. In this review, we have systemically reviewed the pathogenesis of IBD and highlighted recent advances in host genetic factors, gut microbiota, and environmental factors and, especially, in abnormal innate and adaptive immune responses and their interactions, which may hold the keys to identify novel predictive or prognostic biomarkers and develop new therapies.

γδ T Cells Link Innate and Adaptive Immune Responses

Chemical Immunology and Allergy - Mechanisms of Epithelial Defense ◽

10.1159/000086659 ◽

2005 ◽

pp. 151-183 ◽

Cited By ~ 153

Author(s):

Wolfgang Holtmeier ◽

Dieter Kabelitz

Keyword(s):

T Cells ◽

Immune Responses ◽

Gamma Delta T Cells ◽

Gamma Delta ◽

Mast cells and γδ T cells are largely dispensable for adaptive immune responses after laser-mediated epicutaneous immunization

Vaccine ◽

10.1016/j.vaccine.2019.11.051 ◽

2020 ◽

Vol 38 (5) ◽

pp. 1015-1024

Author(s):

Isabella A. Joubert ◽

Daniel Kovacs ◽

Sandra Scheiblhofer ◽

Petra Winter ◽

Evgeniia Korotchenko ◽

...

Keyword(s):

T Cells ◽

Mast Cells ◽

Immune Responses ◽

Γδ T Cells ◽

Priming with FLO8-deficient Candida albicans induces Th1-biased protective immunity against lethal polymicrobial sepsis

Cellular and Molecular Immunology ◽

10.1038/s41423-020-00576-6 ◽

2020 ◽

Author(s):

Quan-Zhen Lv ◽

De-Dong Li ◽

Hua Han ◽

Yi-Heng Yang ◽

Jie-Lin Duan ◽

...

Keyword(s):

T Cells ◽

Candida Albicans ◽

Immune Responses ◽

Protective Immunity ◽

Cecal Ligation ◽

Protective Effects ◽

Naive T Cells ◽

Naïve T Cells ◽

Continuous Output ◽

Induced Apoptosis

Abstract The morphological switch between yeast and hyphae of Candida albicans is essential for its interaction with the host defense system. However, the lack of understanding of host–pathogen interactions during C. albicans infection greatly hampers the development of effective immunotherapies. Here, we found that priming with the C. albicans FLO8-deficient (flo8) mutant, locked in yeast form, protected mice from subsequent lethal C. albicans infection. Deficiency of Dectin-2, a fungus-derived α-mannan recognition receptor, completely blocked flo8 mutant-induced protection. Mechanistically, the flo8 mutant-induced Dectin-2/CARD9-mediated IL-10 production in DCs and macrophages to block thymus atrophy by inhibiting the C. albicans-induced apoptosis of thymic T cells, which facilitated the continuous output of naive T cells from the thymus to the spleen. Continuous recruitment of naive T cells to the spleen enhanced Th1-biased antifungal immune responses. Consequently, depletion of CD4+ T cells or blockade of IL-10 receptor function using specific antibodies in mice completely blocked the protective effects of flo8 mutant priming against C. albicans infection. Moreover, mannans exposed on the surface of the flo8 mutant were responsible for eliciting protective immunity by inhibiting the C. albicans-induced apoptosis of thymic T cells to sustain the number of naive T cells in the spleen. Importantly, priming with the flo8 mutant extensively protected mice from polymicrobial infection caused by cecal ligation and puncture (CLP) by enhancing Th1-biased immune responses. Together, our findings imply that targeting FLO8 in C. albicans elicits protective immune responses against polymicrobial infections and that mannans extracted from the flo8 mutant are potential immunotherapeutic candidate(s) for controlling infectious diseases.

CD154:CD40 Co-Stimulatory Blockade: A Novel Approach To Prevent Sensitization to Donor Alloantigens.

Blood ◽

10.1182/blood.v106.11.1273.1273 ◽

2005 ◽

Vol 106 (11) ◽

pp. 1273-1273

Author(s):

Hong Xu ◽

Jun Yan ◽

Suzanne T. Ildstad

Keyword(s):

T Cells ◽

Immune Responses ◽

B Cell ◽

Germinal Center ◽

Cell Activation ◽

Cell Tolerance ◽

B Cell Activation ◽

B Cell Tolerance ◽

Abstract Introduction: Recipient sensitization is one of the most critical problems facing clinical transplantation. Allosensitized recipients often rapidly reject vascularized solid organ grafts as a result of preformed anti-donor antibody. Similarly, bone marrow transplantation for sickle cell disease and thalassemia is limited by sensitization from transfusion. A method to prevent sensitization would have a significant impact on transplant outcomes. Until recently, T cells were believed to be the primary effector cell in the induction of adaptive immune responses. We recently found that humoral immunity provides a dominant barrier in allosensitization to MHC antigens. B cell activation occurs through T-cell-dependent responses via signaling from the co-stimulatory molecule CD154 (on T cells) to its ligand CD40 (on B cells). Here, we examined whether blocking the costimulatory interaction between T and B cells during exposure to alloantigen would prevent allosensitization. Materials and Methods: Mice deficient for CD154 molecule (CD154−/ −, H-2b), α β-TCR+ T cells (TCRβ −/ −, H-2b); or wild type B6 (H-2b) mice received allogeneic BALB/c (H-2d) skin grafts (SG) on day 0. Some B6 mice were also treated with anti-CD154 (day0 and day+3) and/or anti-α β-TCR mAb (day-3) peritransplant. Antibodies were detected by flow cytometry cross-match (FCM) assay and reported as mean fluorescence intensity (MFI). Results: CD154−/ − mice rejected primary BALB/c SG with a time course similar to normal B6 controls (12.4 ± 2.1 vs. 12.7 ± 2.4 days). TCRβ −/ − mice accepted SG permanently (>120 days). Notably, anti-donor antibody was not generated in either the CD154−/ − or TCRβ −/ − mice (MFI: 4.1 ± 0.1 and 4.2 ± 0.4) after SG compared with Ab in naïve serum (3.0±0.2). Sensitized B6 mice had significantly higher antibody titers (106.8 ± 35.1) 4 weeks after SG rejection. A second SG transplanted 5 to 7 weeks after the first graft was rejected at an accelerated rate (9.0 ± 0.8 days, P < 0.05) in the CD154−/ − mice, but no anti-donor MHC antibody was produced. Second grafts placed on TCRβ −/ − mice were accepted, as were the primary SG. In normal B6 recipients pretreated with anti-CD154 or anti-α β-TCR alone, SG survival was not significantly prolonged. The Ab titers were only slightly higher in mice treated with anti-CD154 (5.9±3.4; P>0.05) than in naïve mice, and significantly higher in mice treated with mAb anti-α β-TCR (45.1±25.6; P=0.03). The combined treatment with both mAbs resulted in complete abrogation of Ab production (4.2±0.9) and 70% of skin grafts survived >100 days. Germinal center formation, reflective of B cell activation, was completely disrupted in mice treated with anti-CD154 alone or combined with anti-α β-TCR. Conclusion: These results suggest that the CD40/CD154 co-stimulatory pathway is critically important in B cell activation to generate alloantibody. Notably, blocking molecular interactions between CD40/CD154 abrogated the generation of antibody and blocked germinal center formation, inducing B cell tolerance. The additional removal of recipient T cells in the context of co-stimulatory blockade resulted in the induction of T as well as B cell tolerance. These findings are the first demonstration that sensitization can be prevented through blockade of co-stimulatory interactions in the generation of adaptive immune responses and could have a significant impact on management of sensitized recipients in the clinic.