Chlamydia pneumoniae infection of monocytes in vitro stimulates innate and adaptive immune responses relevant to those in Alzheimer’s disease

Earlier investigations have revealed a surprising complexity and variety in the range of interaction between cells of the innate and adaptive immune system. Our understanding of the specialized roles of dendritic cell (DC) subsets in innate and adaptive immune responses has been significantly advanced over the years. Because of their immunoregulatory capacities and because very small numbers of activated DC are highly efficient at generating immune responses against antigens, DCs have been vigorously used in clinical trials in order to elicit or amplify immune responses against cancer and chronic infectious diseases. A better insight in DC immunobiology and function has stimulated many new ideas regarding the potential ways forward to improve DC therapy in a more fundamental way. Here, we discuss the continuous search for optimal in vitro conditions in order to generate clinical-grade DC with a potent immunogenic potential. For this, we explore the molecular and cellular mechanisms underlying adequate immune responses and focus on most favourable DC culture regimens and activation stimuli in humans. We envisage that by combining each of the features outlined in the current paper into a unified strategy, DC-based vaccines may advance to a higher level of effectiveness.

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In Vitro Platform Establishes Antigen-Specific CD8+ T Cell Cytotoxicity to Encapsulated Cells via Indirect Antigen Recognition

10.1101/2019.12.11.872978 ◽

2019 ◽

Author(s):

Ying Li ◽

Anthony W. Frei ◽

Ethan Y. Yang ◽

Irayme Labrada-Miravet ◽

Chuqiao Sun ◽

...

Keyword(s):

T Cell ◽

Immune Responses ◽

T Cell Activation ◽

Cell Activation ◽

Immune Recognition ◽

Adaptive Immune Responses ◽

Activated T Cells ◽

Encapsulated Cells ◽

Adaptive Immune

AbstractCell replacement therapy has the potential to cure diseases caused by the absence or malfunction of specialized cells. A substantial impediment to the success of any non-autologous cellular transplant is the need for systemic immunosuppressive drugs to prevent host-mediated rejection of the foreign cells. Cellular encapsulation, i.e., the entrapment of cells within stable polymeric hydrogels, has been clinically explored to prevent host immune recognition and attack, but the efficacy of these encapsulated grafts is poor. While several studies have explored improvements in innate immune acceptance of these encapsulated cells, little attention has been paid to the roles of adaptive immune responses, specifically graft-targeting T cell activation, in graft destabilization. Herein, we established an efficient, single-antigen in vitro platform capable of delineating direct and indirect host T cell recognition to microencapsulated cellular grafts and evaluating their consequential impacts. Using alginate as the model hydrogel, encapsulated membrane-bound ovalbumin (mOVA) stimulator cells were incubated with antigen-specific OTI lymphocytes and subsequent OVA-specific CD8+ T cell activation and effector function were quantified. We established that alginate microencapsulation abrogates direct T cell activation by interrupting donor-host interaction; however, indirect T cell activation mediated by host antigen presenting cells (APCs) primed with shed donor antigens still occurs. These activated T cells imparted cytotoxicity on the encapsulated cells, likely via diffusion of cytotoxic solutes. Overall, this platform delivers unique mechanistic insight into the impacts of hydrogel encapsulation on host adaptive immune responses, as well as a tool for the efficient immune screening on new encapsulation methods and/or synergistic immunomodulatory agents.

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Morinda citrifolianoni water extract enhances innate and adaptive immune responses in healthy mice, ex vivo, and in vitro

Phytotherapy Research ◽

10.1002/ptr.6256 ◽

2019 ◽

Vol 33 (3) ◽

pp. 676-689 ◽

Cited By ~ 4

Author(s):

Yo Han Hong ◽

Young-Su Yi ◽

Sang Yun Han ◽

Nur Aziz ◽

Han Gyung Kim ◽

...

Keyword(s):

Immune Responses ◽

Ex Vivo ◽

Water Extract ◽

Adaptive Immune Responses ◽

Adaptive Immune

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Intestinal CD103+, but not CX3CR1+, antigen sampling cells migrate in lymph and serve classical dendritic cell functions

Journal of Experimental Medicine ◽

10.1084/jem.20091925 ◽

2009 ◽

Vol 206 (13) ◽

pp. 3101-3114 ◽

Cited By ~ 475

Author(s):

Olga Schulz ◽

Elin Jaensson ◽

Emma K. Persson ◽

Xiaosun Liu ◽

Tim Worbs ◽

...

Keyword(s):

Immune Responses ◽

Direct Injection ◽

Turnover Rates ◽

Mesenteric Lymph Nodes ◽

Adaptive Immune Responses ◽

Cell Functions ◽

Adaptive Immune ◽

Inflammatory Conditions

Chemokine receptor CX3CR1+ dendritic cells (DCs) have been suggested to sample intestinal antigens by extending transepithelial dendrites into the gut lumen. Other studies identified CD103+ DCs in the mucosa, which, through their ability to synthesize retinoic acid (RA), appear to be capable of generating typical signatures of intestinal adaptive immune responses. We report that CD103 and CX3CR1 phenotypically and functionally characterize distinct subsets of lamina propria cells. In contrast to CD103+ DC, CX3CR1+ cells represent a nonmigratory gut-resident population with slow turnover rates and poor responses to FLT-3L and granulocyte/macrophage colony-stimulating factor. Direct visualization of cells in lymph vessels and flow cytometry of mouse intestinal lymph revealed that CD103+ DCs, but not CX3CR1-expressing cells, migrate into the gut draining mesenteric lymph nodes (LNs) under steady-state and inflammatory conditions. Moreover, CX3CR1+ cells displayed poor T cell stimulatory capacity in vitro and in vivo after direct injection of cells into intestinal lymphatics and appeared to be less efficient at generating RA compared with CD103+ DC. These findings indicate that selectively CD103+ DCs serve classical DC functions and initiate adaptive immune responses in local LNs, whereas CX3CR1+ populations might modulate immune responses directly in the mucosa and serve as first line barrier against invading enteropathogens.

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Adaptive immune responses during Shigella dysenteriae type 1 infection: an in vitro stimulation with 57 kDa major antigenic OMP in the presence of anti-CD3 antibody

Molecular and Cellular Biochemistry ◽

10.1007/s11010-009-0314-z ◽

2009 ◽

Vol 338 (1-2) ◽

pp. 1-10 ◽

Cited By ~ 1

Author(s):

Ashim Kumar Bagchi ◽

Ajoy Kumar Sinha ◽

Rushita Adhikari ◽

Joydeep Mukherjee

Keyword(s):

Immune Responses ◽

Shigella Dysenteriae ◽

Adaptive Immune Responses ◽

Adaptive Immune ◽

Shigella Dysenteriae Type

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Potential efficacy of dendritic cell immunomodulation in the treatment of osteoarthritis

Rheumatology ◽

10.1093/rheumatology/keaa745 ◽

2020 ◽

Author(s):

Murad Alahdal ◽

Hui Zhang ◽

Rongxiang Huang ◽

Wei Sun ◽

Zhiqin Deng ◽

...

Keyword(s):

Synovial Fluid ◽

Immune Responses ◽

Peripheral Tolerance ◽

Adaptive Immune Responses ◽

Adaptive Immune ◽

Promising Tool ◽

Potential Efficacy ◽

Plasmacytoid Dcs ◽

Antigen Presenting

Abstract Dendritic cells (DCs) are a cluster of heterogeneous antigen-presenting cells that play a pivotal role in both innate and adaptive immune responses. Rare reports have discussed their role in OA immunopathogenesis. Recently, DCs derived from the synovial fluid of OA mice were shown to have increased expression of toll-like receptors. Moreover, from in vitro studies it was concluded that DCs derived from OA patients had secreted high levels of inflammatory cytokines. Likewise, a significant increase in CD123+BDCA-2 plasmacytoid DCs has been observed in the synovial fluid of OA patients. Furthermore, DCs have a peripheral tolerance potential and can become regulatory under specific circumstances. This could be exploited as a promising tool to eliminate immunoinflammatory manifestations in OA disease. In this review, the potential roles DCs could play in OA pathogenesis have been described. In addition, suggestions for the development of new immunotherapeutic strategies involving intra-articular injections of tolerogenic plasmacytoid DCs for treating OA inflammations have been made.

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Undaria pinnatifida Fucoidan-Rich Extract Induces Both Innate and Adaptive Immune Responses

Natural Product Communications ◽

10.1177/1934578x19873724 ◽

2019 ◽

Vol 14 (8) ◽

pp. 1934578X1987372

Author(s):

Hwan H. Lee ◽

Yoo J. Cho ◽

Daeung Yu ◽

Donghwa Chung ◽

Gun-Hee Kim ◽

...

Keyword(s):

Immune Responses ◽

Cd8 T Cells ◽

Undaria Pinnatifida ◽

Plasma Concentrations ◽

Adaptive Immune Responses ◽

Adaptive Immune ◽

Tnf Α ◽

Ifn Γ

Fucoidans are widely used as an ingredient of dietary supplements. We investigated the immune stimulatory activities of Undaria pinnatifida ( Alariaceae) fucoidan-rich extract (UPF-RE) in vitro as well as in vivo . In vitro, the extract stimulated Raw 264.7 cells to produce significant nitric oxide (NO) metabolites and cytokines (TNF-α, IL-1α, IL-1β, and IL-6). It also induced the proliferation of primary mouse splenocytes and the secretion of IL-4, which correlated with the phosphorylation of Extracellular-signal-regulated kinase (ERK) protein. In in vivo experiments, first, 50 mg/kg of 3 different types of UPF-RE, DSU02, DSU02L (low molecular weight, <3 kDa), and DSU02H (high molecular weight, >10 kDa), were orally administered to C57BL/6 mice. After 14 days, the frequencies of CD3+, CD4+, and CD8+ T cells and NK cells from each group were analyzed. Plasma concentrations of TNF-α and IFN-γ were determined. The frequencies of CD3+ and CD4+ showed a statistically significant increase in splenocytes isolated from the DSU02 and DSU02H groups. Also, there was significant production of TNF-α and IFN-γ from the DSU02 group. Second, 3 different concentrations of DSU02 (50, 100, and 150 mg/kg) were orally administered. After 14 days, the proliferative capacity of CD3+, CD4+, and CD8+ T cells was investigated, and the plasma concentrations of IgM and total IgG were determined. Plasma concentration of IgM from the DSU02 150 mg/kg group was statistically significantly higher compared with that from the other groups. We suggest that UPF-RE could be a good candidate for a natural immune stimulator to induce innate as well as adaptive immune responses.

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Thymosin alpha-1 Protected T Cells from Excessive Activation in Severe COVID-19

10.21203/rs.3.rs-25869/v2 ◽

2020 ◽

Author(s):

Kuai Yu ◽

Yongjian Wu ◽

Jingjing He ◽

Xuefei Liu ◽

Bo Wei ◽

...

Keyword(s):

T Cells ◽

Immune Responses ◽

Adaptive Immunity ◽

Adaptive Immune Responses ◽

Activated T Cells ◽

T Effector Cells ◽

Adaptive Immune ◽

The Impact ◽

Excessive Activation

Abstract Two typical features of uncontrolled inflammation, cytokine storm and lymphopenia, are associated with the severity of coronavirus disease 2019 (COVID-19), demonstrating that both innate and adaptive immune responses are involved in the development of this disease. Recent studies have explored the contribution of innate immune cells to the pathogenesis of the infection. However, the impact of adaptive immunity on this disease remains unknown. In order to clarify the role of adaptive immune response in COVID-19, we characterized the phenotypes of lymphocytes in PBMCs from patients at different disease stages using single-cell RNA sequencing (scRNA-seq) technology. Dynamics of the effector cell levels in lymphocytes revealed a distinct feature of adaptive immunity in severely affected patients, the coincidence of impaired cellular and enhanced humoral immune responses, suggesting that dysregulated adaptive immune responses advanced severe COVID-19. Excessive activation and exhaustion were observed in CD8 T effector cells, which might contribute to the lymphopenia. Interestingly, expression of Prothymosin alpha (PTMA), the proprotein of Tα1, was significantly increased in a group of CD8 T memory stem cells, but not in excessively activated T cells. We further showed that Tα1 significantly promoted the proliferation of activated T cells in vitro and relieved the lymphopenia in COVID-19 patients. Our data suggest that protection of T cells from excessive activation might be critical for the prevention of severe COVID-19.

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