scholarly journals The Interleukins Orchestrate Mucosal Immune Responses to Salmonella Infection in the Intestine

Cells ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 3492
Author(s):  
Fu-Chen Huang
Keyword(s):  
Innate Immunity ◽  
Immune Responses ◽  
Natural Killer ◽  
Adaptive Immunity ◽  
Alternative Therapy ◽  
Muramyl Dipeptide ◽  
Protective Effects ◽  
Salmonella Infection ◽  
Intestinal Pathogens ◽  
Anti Inflammatory

Salmonella infection remains one of the major public health problems in the world, with increasing resistance to antibiotics. The resolution is to explore the pathogenesis of the infection and search for alternative therapy other than antibiotics. Immune responses to Salmonella infection include innate and adaptive immunity. Flagellin or muramyl dipeptide from Salmonella, recognized by extracellular Toll-like receptors and intracellular nucleotide-binding oligomerization domain2, respectively, induce innate immunity involving intestinal epithelial cells, neutrophils, macrophages, dendric cells and lymphocytes, including natural killer (NK) and natural killer T (NKT) cells. The cytokines, mostly interleukins, produced by the cells involved in innate immunity, stimulate adaptive immunity involving T and B cells. The mucosal epithelium responds to intestinal pathogens through its secretion of inflammatory cytokines, chemokines, and antimicrobial peptides. Chemokines, such as IL-8 and IL-17, recruit neutrophils into the cecal mucosa to defend against the invasion of Salmonella, but induce excessive inflammation contributing to colitis. Some of the interleukins have anti-inflammatory effects, such as IL-10, while others have pro-inflammatory effects, such as IL-1β, IL-12/IL-23, IL-15, IL-18, and IL-22. Furthermore, some interleukins, such as IL-6 and IL-27, exhibit both pro- and anti-inflammatory functions and anti-microbial defenses. The majority of interleukins secreted by macrophages and lymphocytes contributes antimicrobial defense or protective effects, but IL-8 and IL-10 may promote systemic Salmonella infection. In this article, we review the interleukins involved in Salmonella infection in the literature.

scholarly journals Interleukin-2 from Adaptive T Cells Enhances Natural Killer Cell Activity against Human Cytomegalovirus-Infected Macrophages

2015 ◽  
Vol 89 (12) ◽  
pp. 6435-6441 ◽  
Author(s):  
Zeguang Wu ◽  
Giada Frascaroli ◽  
Carina Bayer ◽  
Tatjana Schmal ◽  
Thomas Mertens
Keyword(s):  
Innate Immunity ◽  
T Cells ◽  
T Cell ◽  
Nk Cells ◽  
Natural Killer ◽  
Adaptive Immunity ◽  
Human Cytomegalovirus ◽  
Latent Infection ◽  
Immune Surveillance ◽  
Interleukin 2

ABSTRACTControl of human cytomegalovirus (HCMV) requires a continuous immune surveillance, thus HCMV is the most important viral pathogen in severely immunocompromised individuals. Both innate and adaptive immunity contribute to the control of HCMV. Here, we report that peripheral blood natural killer cells (PBNKs) from HCMV-seropositive donors showed an enhanced activity toward HCMV-infected autologous macrophages. However, this enhanced response was abolished when purified NK cells were applied as effectors. We demonstrate that this enhanced PBNK activity was dependent on the interleukin-2 (IL-2) secretion of CD4+T cells when reexposed to the virus. Purified T cells enhanced the activity of purified NK cells in response to HCMV-infected macrophages. This effect could be suppressed by IL-2 blocking. Our findings not only extend the knowledge on the immune surveillance in HCMV—namely, that NK cell-mediated innate immunity can be enhanced by a preexisting T cell antiviral immunity—but also indicate a potential clinical implication for patients at risk for severe HCMV manifestations due to immunosuppressive drugs, which mainly suppress IL-2 production and T cell responsiveness.IMPORTANCEHuman cytomegalovirus (HCMV) is never cleared by the host after primary infection but instead establishes a lifelong latent infection with possible reactivations when the host′s immunity becomes suppressed. Both innate immunity and adaptive immunity are important for the control of viral infections. Natural killer (NK) cells are main innate effectors providing a rapid response to virus-infected cells. Virus-specific T cells are the main adaptive effectors that are critical for the control of the latent infection and limitation of reinfection. In this study, we found that IL-2 secreted by adaptive CD4+T cells after reexposure to HCMV enhances the activity of NK cells in response to HCMV-infected target cells. This is the first direct evidence that the adaptive T cells can help NK cells to act against HCMV infection.

scholarly journals Early Innate Immunity to Bacterial Infection in the Lung Is Regulated Systemically by the Commensal Microbiota via Nod-Like Receptor Ligands

2014 ◽  
Vol 82 (11) ◽  
pp. 4596-4606 ◽  
Author(s):  
Thomas B. Clarke
Keyword(s):  
Innate Immunity ◽  
Bacterial Infection ◽  
Muramyl Dipeptide ◽  
Upper Respiratory Tract ◽  
Host Defenses ◽  
Receptor Ligands ◽  
Content Type ◽  
Commensal Microbiota ◽  
Intestinal Pathogens ◽  
Upper Respiratory

ABSTRACTThe commensal microbiota is a major regulator of the immune system. The majority of commensal bacteria inhabit the gastrointestinal tract and are known to regulate local mucosal defenses against intestinal pathogens. There is growing appreciation that the commensal microbiota also regulates immune responses at extraintestinal sites. Currently, however, it is unclear how this influences host defenses against bacterial infection outside the intestine. Microbiota depletion caused significant defects in the early innate response to lung infection by the major human pathogenKlebsiella pneumoniae. After microbiota depletion, early clearance ofK. pneumoniaewas impaired, and this could be rescued by administration of bacterial Nod-like receptor (NLR) ligands (the NOD1 ligand MurNAcTriDAPand NOD2 ligand muramyl dipeptide [MDP]) but not bacterial Toll-like receptor (TLR) ligands. Importantly, NLR ligands from the gastrointestinal, but not upper respiratory, tract rescued host defenses in the lung. Defects in early innate immunity were found to be due to reduced reactive oxygen species-mediated killing of bacteria by alveolar macrophages. These data show that bacterial signals from the intestine have a profound influence on establishing the levels of antibacterial defenses in distal tissues.

scholarly journals Roles of Innate and Adaptive Immunity in Respiratory Mycoplasmosis

1998 ◽  
Vol 66 (8) ◽  
pp. 3485-3491 ◽  
Author(s):  
Samuel C. Cartner ◽  
J. Russell Lindsey ◽  
Julie Gibbs-Erwin ◽  
Gail H. Cassell ◽  
Jerry W. Simecka
Keyword(s):  
Innate Immunity ◽  
Immune Responses ◽  
Adaptive Immunity ◽  
Humoral Immunity ◽  
Lung Lesion ◽  
Scid Mice ◽  
Current Evidence ◽  
Innate And Adaptive Immunity ◽  
Lung Lesions ◽  
Multiple Organs

ABSTRACT Current evidence suggests that host defense in respiratory mycoplasmosis is dependent on both innate and humoral immunity. To further delineate the roles of innate and adaptive immunity in antimycoplasmal defenses, we intranasally infected C3H/HeSnJ-scid/scid (C3H-SCID), C3H/HeSnJ (C3H), C57BL/6J-scid/scid (C57-SCID), and C57BL/6N (C57BL) mice with Mycoplasma pulmonis and at 14 and 21 days postinfection performed quantitative cultures of lungs and spleens, quantification of lung lesions, and histopathologic assessments of all other major organs. We found that numbers of mycoplasmas in lungs were associated with genetic background (C3H susceptible, C57BL resistant) rather than functional state of adaptive immunity, indicating that innate immunity is the main contributor to antimycoplasmal defense of the lungs. Extrapulmonary dissemination of mycoplasmas with colonization of spleens and histologic lesions in multiple organs was a common occurrence in all mice. The absence of adaptive immune responses in severe combined immunodeficient (SCID) mice resulted in increased mycoplasmal colonization of spleens and lesions in extrapulmonary sites, particularly spleens, hearts, and joints, and also reduced lung lesion severity. The transfer of anti-M. pulmonis serum to infected C3H-SCID mice prevented extrapulmonary infection and disease, while the severity of lung lesions was restored by transfer of naive spleen cells to infected C3H-SCID mice. Collectively, our results strongly support the conclusions that innate immunity provides antimycoplasmal defense of the lungs and humoral immunity has the major role in defense against systemic dissemination of mycoplasmal infection, but cellular immune responses may be important in exacerbation of mycoplasmal lung disease.

scholarly journals Trained Immunity as an Adaptive Branch of Innate Immunity

2021 ◽  
Vol 22 (19) ◽  
pp. 10684
Author(s):  
Vaclav Vetvicka ◽  
Petr Sima ◽  
Luca Vannucci
Keyword(s):  
Innate Immunity ◽  
Life Span ◽  
Nk Cells ◽  
Natural Killer ◽  
Adaptive Immunity ◽  
Epigenetic Reprogramming ◽  
Immunocompetent Cells ◽  
Infectious Agents ◽  
Immune Reactions ◽  
Trained Immunity

The concept of trained immunity has become one of the most interesting and potentially commercially and clinically relevant ideas of current immunology. Trained immunity is realized by the epigenetic reprogramming of non-immunocompetent cells, primarily monocytes/macrophages and natural killer (NK) cells, and is less specific than adaptive immunity; therefore, it may cross-protect against other infectious agents. It remains possible, however, that some of the observed changes are simply caused by increased levels of immune reactions resulting from supplementation with immunomodulators, such as glucan. In addition, the question of whether we can talk about trained immunity in cells with a life span of only few days is still unresolved.

scholarly journals Human natural killer cells mediate adaptive immunity to viral antigens

2019 ◽  
Vol 4 (35) ◽  
pp. eaat8116 ◽  
Author(s):  
Rana Nikzad ◽  
Laura S. Angelo ◽  
Kevin Aviles-Padilla ◽  
Duy T. Le ◽  
Vipul K. Singh ◽  
...  
Keyword(s):  
Immune Responses ◽  
Nk Cells ◽  
Natural Killer ◽  
Adaptive Immunity ◽  
Human Memory ◽  
Humanized Mice ◽  
Adaptive Immune Responses ◽  
Adaptive Immune ◽  
Human Volunteers

Adaptive immune responses are defined as antigen sensitization–dependent and antigen-specific responses leading to establishment of long-lived immunological memory. Although natural killer (NK) cells have traditionally been considered cells of the innate immune system, mounting evidence in mice and nonhuman primates warrants reconsideration of the existing paradigm that B and T cells are the sole mediators of adaptive immunity. However, it is currently unknown whether human NK cells can exhibit adaptive immune responses. We therefore tested whether human NK cells mediate adaptive immunity to virally encoded antigens using humanized mice and human volunteers. We found that human NK cells displayed vaccination-dependent, antigen-specific recall responses in vitro, when isolated from livers of humanized mice previously vaccinated with HIV-encoded envelope protein. Furthermore, we discovered that large numbers of cytotoxic NK cells with a tissue-resident phenotype were recruited to sites of varicella-zoster virus (VZV) skin test antigen challenge in VZV-experienced human volunteers. These NK-mediated recall responses in humans occurred decades after initial VZV exposure, demonstrating that NK memory in humans is long-lived. Our data demonstrate that human NK cells exhibit adaptive immune responses upon vaccination or infection. The existence of human memory NK cells may allow for the development of vaccination-based approaches capable of establishing potent NK-mediated memory functions contributing to host protection.

scholarly journals The cGAS-STING Pathway: A Promising Immunotherapy Target

2021 ◽  
Vol 12 ◽  
Author(s):  
Liang Ou ◽  
Ao Zhang ◽  
Yuxing Cheng ◽  
Ying Chen
Keyword(s):  
Innate Immunity ◽  
T Lymphocytes ◽  
Immune Responses ◽  
Adaptive Immunity ◽  
Inflammatory Diseases ◽  
Macrophage Polarization ◽  
Signal Pathway ◽  
Autoimmune And Inflammatory Diseases ◽  
Immunotherapy Target ◽  
Sting Pathway

With the continuous development of immunotherapy, researchers have paid more attention to the specific immune regulatory mechanisms of various immune responses in different diseases. As a novel and vital innate immune signal pathway, the cGAS-STING signal pathway activated by nucleic acid substances, interplays with other immune responses, by which it participates in regulating cancer, autoimmune and inflammatory diseases, microbial and parasitic infectious diseases, and other diseases. With the exception of its role in innate immunity, the growing list of researches demonstrated expanding roles of the cGAS-STING signal pathway in bridging the innate immunity (macrophage polarization) with the adaptive immunity (T lymphocytes differentiation). Macrophages and T lymphocytes are the most representative cells of innate immunity and adaptive immunity, respectively. Their polarization or differentiation are involved in the pathogenesis and progression of various diseases. Here we mainly summarized recent advanced discoveries of how the cGAS-STING signal pathway regulated macrophages polarization and T lymphocytes differentiation in various diseases and vaccine applications, providing a promising direction for the development and clinical application of immunotherapeutic strategies for related diseases.

More than just innate affairs – on the role of annexins in adaptive immunity

2016 ◽  
Vol 397 (10) ◽  
pp. 1017-1029 ◽  
Author(s):  
Heiko Weyd
Keyword(s):  
T Cell ◽  
Immune Responses ◽  
Adaptive Immunity ◽  
Immune Cells ◽  
Cell Types ◽  
Innate Immune ◽  
Innate Immune Cells ◽  
Direct Role ◽  
Cytokine Milieu ◽  
Anti Inflammatory

Abstract In more than 30 years of research annexins have been demonstrated to regulate immune responses. The prototype member of this family, annexin (Anx) A1, has been widely recognized as an anti-inflammatory mediator affecting migration and cellular responses of various cell types of the innate immune system. Evidently, effects on innate immune cells also impact on the course of adaptive immune responses. Innate immune cells provide a distinct cytokine milieu during initiation of adaptive immunity which regulates the development of T cell responses. Moreover, innate immune cells such as monocytes can differentiate into dendritic cells and take an active part in T cell stimulation. Accumulating evidence shows a direct role for annexins in adaptive immunity. Anx A1, the annexin protein studied in most detail, has been shown to influence antigen presentation as well as T cells directly. Moreover, immune modulatory roles have been described for several other annexins such as Anx A2, Anx A4, Anx A5 and Anx A13. This review will focus on the involvement of Anx A1 and other annexins in central aspects of adaptive immunity, such as recruitment and activation of antigen presenting cells, T cell differentiation and the anti-inflammatory removal of apoptotic cells.

scholarly journals ID2006 Crosstalk between effector cells of adaptive immunity and mesenchymal stromal cells

2017 ◽  
Vol 4 (S) ◽  
pp. 38
Author(s):  
Aleksandra Gornostaeva
Keyword(s):  
Innate Immunity ◽  
Adaptive Immunity ◽  
Mesenchymal Stromal Cells ◽  
Immune Cells ◽  
Stromal Cells ◽  
Feedback Loop ◽  
Inflammatory Phenotype ◽  
Innate Immunity Cells ◽  
Immunomodulatory Properties ◽  
Anti Inflammatory

Multipotent mesenchymal stromal cells (MSCs) are a perspective tool for regenerative medicine due low immunogenicity and immunomodulation. The "feedback loop" exists in MSC/immune cells relationships, when "inflammatory" stimulation switches immunoregulaton by MSCs. Currently, the most studied effect of allogeneic MSCs on adaptive immunity cells, mainly on T lymphocytes. Studies of the interaction of MSCs and innate immunity cells are much less. "Reverse effects" (the effect of immune cells on MSCs) are virtually not investigated. Initiation of the inflammation occurs with activation of innate immunity cells, that "turns on" immunomodulatory properties. In this regard, the study of the interaction of MSCs and monocytes is particularly relevant. MSCs from human adipose tissue and CD14+monocytes (MNs) from peripheral blood of healthy volunteers were used. To stimulate monocytes conditioned medium (CM) after 72 hours of mixed lymphocyte reaction (MLR) was applied. This CM was enriched with IL-8, INF-gamma and TNF-a.  Optimization of MN activation procedure was performed prior to experiments. CD14+MNs were incubated with different concentration of MLR-CM for a different time. The activation and viability of MNs was evaluated every 24 hours. The overnight exposure of MNs to 3-day 50% CM-MLR was found to be optimum regime. We studied the of MSC/monocyte interaction paying special attention to "feedback loop".  In the presence of activated MNs, MSCs possessed unchanged viability (96%), transmembrane mitochondria potential, ROS level and twice reduced lysosome activity. The cytokine profile in coculture medium was changed significantly. IL-6 and MCP-1 were increased vs monocultures of both cell types. IL-8 was similar to MN monoculture. TNF alpha, MIG, IL-10 were detected as tracers. Elevation of IL-6 and MIG indicates on acquisition of anti-inflammatory phenotype by MSCs. After interaction with MSC, the share of CD69+ MNs (nonspecific marker of early activation) decreased, HLA-DR (MHC class II receptor) increased slightly. A threefold increase in both CD163+ MN’s share and MFI was detected, whereas CD86 antigen was not expressed. The changes in the cytokine profile and the expression of surface markers described above are characteristic of the anti-inflammatory phenotype of monocytes.  Thus, upon interaction MSC exhibited pronounced immunomodulatory properties and shifted the phenotype of monocytes towards the anti-inflammatory. These data indicate on the MSC potential to modulate early stages of inflammation, while retaining their functional state.

scholarly journals SARS-COV-2 Vaccines Immunological Impact

2021 ◽  
Author(s):  
Hatem Tallima ◽  
Rashika El Ridi
Keyword(s):  
Innate Immunity ◽  
Immune Responses ◽  
Cytotoxic T Cells ◽  
Large Fraction ◽  
Killer Cell ◽  
Acquired Immunity ◽  
Protective Effects ◽  
Spike Glycoprotein ◽  
Adverse Side Effects ◽  
Life Threatening

The immune responses to SARS-CoV-2 are herein detailed to clarify the innate immunity protective effects in a large fraction of individuals exposed to the infection, and the drawbacks of the interference of the acquired immunity cytotoxic T cells and antibody-dependent natural killer cell-mediated cytotoxicity arms. Very precisely, the available vaccines based on full-length spike glycoprotein in a mRNA or DNA-based construct, or whole virus potently lead to generation of these immunologically damaging effectors, especially following exposure to the pathogen. Conversely, a vaccine exclusively based on spike glycoprotein subunit 1 in a protein form can protect against the life-threatening virus infection and never lead to adverse side effects.

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