scholarly journals Vaccination with Alpha-Gal Protects Against Mycobacterial Infection in the Zebrafish Model of Tuberculosis

Vaccines ◽  
2020 ◽  
Vol 8 (2) ◽  
pp. 195 ◽  
Author(s):  
Iván Pacheco ◽  
Marinela Contreras ◽  
Margarita Villar ◽  
María Angeles Risalde ◽  
Pilar Alberdi ◽  
...  
Keyword(s):  
Immune Response ◽  
Mycobacterial Infection ◽  
Antagonistic Effect ◽  
Protective Mechanisms ◽  
Zebrafish Model ◽  
Tick Saliva ◽  
Macrophage Response ◽  
B Cell Maturation ◽  
Delayed Anaphylaxis ◽  
Mammalian Meat

The alpha-Gal syndrome (AGS) is associated with tick bites that can induce in humans high levels of IgE antibodies against the carbohydrate Galα1-3Galβ1-(3)4GlcNAc-R (α-Gal) present in glycoproteins and glycolipids from tick saliva that mediate primarily delayed anaphylaxis to mammalian meat consumption. It has been proposed that humans evolved by losing the capacity to synthesize α-Gal to increase the protective immune response against pathogens with this modification on their surface. This evolutionary adaptation suggested the possibility of developing vaccines and other interventions to induce the anti-α-Gal IgM/IgG protective response against pathogen infection and multiplication. However, the protective effect of the anti-α-Gal immune response for the control of tuberculosis caused by Mycobacterium spp. has not been explored. To address the possibility of using vaccination with α-Gal for the control of tuberculosis, in this study, we used the zebrafish-Mycobacterium marinum model. The results showed that vaccination with α-Gal protected against mycobacteriosis in the zebrafish model of tuberculosis and provided evidence on the protective mechanisms in response to vaccination with α-Gal. These mechanisms included B-cell maturation, antibody-mediated opsonization of mycobacteria, Fc-receptor (FcR)-mediated phagocytosis, macrophage response, interference with the α-Gal antagonistic effect of the toll-like receptor 2 (TLR2)/nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB)-mediated immune response, and upregulation of pro-inflammatory cytokines. These results provided additional evidence supporting the role of the α-Gal-induced immune response in the control of infections caused by pathogens with this modification on their surface and the possibility of using this approach for the control of multiple infectious diseases.

scholarly journals Infection-induced miR-126 suppresses tsc1- and cxcl12a-dependent permissive macrophages during mycobacterial infection

2021 ◽  
Author(s):  
Kathryn Wright ◽  
Kumudika de Silva ◽  
Karren M. Plain ◽  
Auriol C. Purdie ◽  
Warwick J. Britton ◽  
...  
Keyword(s):  
Immune Response ◽  
Detrimental Effect ◽  
Mycobacterial Infection ◽  
Protective Role ◽  
Zebrafish Embryos ◽  
Zebrafish Model ◽  
Effector Pathways ◽  
The Impact ◽  
Mtor Signalling

AbstractRegulation of host microRNA (miRNA) expression is a contested node that controls the host immune response to mycobacterial infection. The host must overcome concerted subversive efforts of pathogenic mycobacteria to launch and maintain a protective immune response. Here we examine the role of miR-126 in the zebrafish model of Mycobacterium marinum infection and identify a protective role for this infection-induced miRNA through multiple effector pathways. Specifically, we analyse the impact of the miR-126 knockdown-induced tsc1a and cxcl12a/ccl2/ccr2 signalling axes during early host-M. marinum interactions. We find a strong detrimental effect of tsc1a upregulation that renders zebrafish embryos susceptible to higher bacterial burden and increased cell death despite dramatically higher recruitment of macrophages to the site of infection. We demonstrate that infection-induced miR-126 suppresses tsc1 and cxcl12a expression thus improving macrophage function early in infection, partially through activation of mTOR signalling and strongly through preventing the recruitment of Ccr2+ permissive macrophages, resulting in the recruitment of protective tnfa-expressing macrophages. Together our results demonstrate an important role for infection-induced miR-126 in shaping an effective immune response to M. marinum infection in zebrafish embryos.

scholarly journals The Brilliance of Borrelia: Mechanisms of Host Immune Evasion by Lyme Disease-Causing Spirochetes

Pathogens ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 281
Author(s):  
Cassidy Anderson ◽  
Catherine A. Brissette
Keyword(s):  
Immune Response ◽  
Lyme Disease ◽  
Immune Evasion ◽  
Host Immune Response ◽  
Surface Proteins ◽  
Borrelia Burgdorferi Sensu Lato ◽  
Adaptive Responses ◽  
Tick Saliva ◽  
Vector Borne ◽  
Antimicrobial Peptide Resistance

Lyme disease (LD) has become the most common vector-borne illness in the northern hemisphere. The causative agent, Borrelia burgdorferi sensu lato, is capable of establishing a persistent infection within the host. This is despite the activation of both the innate and adaptive immune responses. B. burgdorferi utilizes several immune evasion tactics ranging from the regulation of surface proteins, tick saliva, antimicrobial peptide resistance, and the disabling of the germinal center. This review aims to cover the various methods by which B. burgdorferi evades detection and destruction by the host immune response, examining both the innate and adaptive responses. By understanding the methods employed by B. burgdorferi to evade the host immune response, we gain a deeper knowledge of B. burgdorferi pathogenesis and Lyme disease, and gain insight into how to create novel, effective treatments.

scholarly journals IL-6 Is Not Absolutely Essential for the Development of a TH17 Immune Response after an Aerosol Infection with Mycobacterium tuberculosis H37rv

Cells ◽  
2020 ◽  
Vol 10 (1) ◽  
pp. 9
Author(s):  
Kristina Ritter ◽  
Jan Christian Sodenkamp ◽  
Alexandra Hölscher ◽  
Jochen Behrends ◽  
Christoph Hölscher
Keyword(s):  
Immune Response ◽  
Inflammatory Diseases ◽  
Mycobacterial Infection ◽  
Minor Effect ◽  
Mycobacterium Tuberculosis H37rv ◽  
Th 17 ◽  
Anti Inflammatory ◽  
A Minor ◽  
Aerosol Infection ◽  
Deficient Mice

Anti-inflammatory treatment of chronic inflammatory diseases often increases susceptibility to infectious diseases such as tuberculosis (TB). Since numerous chronic inflammatory and autoimmune diseases are mediated by interleukin (IL)-6-induced T helper (TH) 17 cells, a TH17-directed anti-inflammatory therapy may be preferable to an IL-12-dependent TH1 inhibition in order to avoid reactivation of latent infections. To assess, however, the risk of inhibition of IL-6-dependent TH17-mediated inflammation, we examined the TH17 immune response and the course of experimental TB in IL-6- and T-cell-specific gp130-deficient mice. Our study revealed that the absence of IL-6 or gp130 on T cells has only a minor effect on the development of antigen-specific TH1 and TH17 cells. Importantly, these gene-deficient mice were as capable as wild type mice to control mycobacterial infection. Together, in contrast to its key function for TH17 development in other inflammatory diseases, IL-6 plays an inferior role for the generation of TH17 immune responses during experimental TB.

scholarly journals Recurring Anaphylaxis: A New Line of Questioning for your HPI

2020 ◽  
Vol 3 (1) ◽  
pp. 18-21
Author(s):  
Wahid Lana ◽  
◽  
Aziz Sameh ◽  
Abraham Christina ◽  
◽  
...  
Keyword(s):  
Allergic Reaction ◽  
Unknown Etiology ◽  
Shortness Of Breath ◽  
Tick Bites ◽  
Ige Antibody ◽  
Delayed Onset ◽  
The Past ◽  
Delayed Anaphylaxis ◽  
Life Threatening ◽  
Mammalian Meat

Anaphylaxis is a serious life-threatening allergic reaction that typically has an immediate onset. It can present as flushing, angioedema, shortness of breath, rash and result in death if not treated immediately. In the past ten years, an emerging cause of delayed anaphylaxis has been identified. An IgE antibody to a mammalian oligosaccharide epitope (alpha-gal, or galactose-alpha-1,3-galactose) has been linked to both immediate and delayed onset anaphylaxis. The immediate form is associated with the first exposure to cetuximab; whereas the delayed onset occurs after ingestion of mammalian meat such as beef and pork. The presentation can develop 2-6 hours after ingestion. This IgE antibody to alpha-gal is strongly suggested that Lone Star tick bites have been the culprit. It is imperative when caring for an anaphylaxis patient of unknown etiology, to consider a line of questioning to not only include recent tick bites, but also last 2-3 meals ingested to identify if mammalian meat may have been the trigger.

scholarly journals The immunomodulatory effect of cathelicidin-B1 on chicken macrophages

2020 ◽  
Vol 51 (1) ◽  
Author(s):  
Lianci Peng ◽  
Maaike R. Scheenstra ◽  
Roel M. van Harten ◽  
Henk P. Haagsman ◽  
Edwin J. A. Veldhuizen
Keyword(s):  
Gene Expression ◽  
Immune Response ◽  
Inflammatory Cytokines ◽  
Culture Conditions ◽  
Titration Calorimetry ◽  
Macrophage Response ◽  
Microbial Infections ◽  
Chicken Macrophage ◽  
Inflammatory Profile ◽  
Pro Inflammatory Cytokines

Abstract Cathelicidins (CATHs) play an important role in the innate immune response against microbial infections. Among the four chicken cathelicidins, CATH-B1 is studied the least. In this study, the effect of CATH-B1 on the macrophage response towards avian pathogenic E. coli (APEC) and bacterial ligands was investigated. Our results show that APEC induced CATH-B1 gene expression in both a chicken macrophage cell line (HD11 cells) and primary macrophages, while expression of the other three CATHs was virtually unaffected. While the antimicrobial activity of CATH-B1 is very low under cell culture conditions, it enhanced bacterial phagocytosis by macrophages. Interestingly, CATH-B1 downregulated APEC-induced gene expression of pro-inflammatory cytokines (IFN-β, IL-1β, IL-6 and IL-8) in primary macrophages. In addition, CATH-B1 pre-incubated macrophages showed a significantly higher gene expression of IL-10 after APEC challenge, indicating an overall anti-inflammatory profile for CATH-B1. Using isothermal titration calorimetry (ITC), CATH-B1 was shown to bind LPS. This suggests that CATH-B1 reduces toll like receptor (TLR) 4 dependent activation by APEC which may partly explain the decreased production of pro-inflammatory cytokines by macrophages. On the contrary, direct binding of CATH-B1 to ODN-2006 enhanced the TLR21 dependent activation of macrophages as measured by nitric oxide production. In conclusion, our results show for the first time that CATH-B1 has several immunomodulatory activities and thereby could be an important factor in the chicken immune response.

Vav-2 signalling participates in the humoral immune response and B cell maturation

2001 ◽  
Vol 29 (5) ◽  
pp. A129-A129
Author(s):  
G. Doody ◽  
S. Bell ◽  
E. Vigorito ◽  
E. Clayton ◽  
S. McAdam ◽  
...  
Keyword(s):  
Immune Response ◽  
B Cell ◽  
Humoral Immune Response ◽  
Cell Maturation ◽  
Humoral Immune ◽  
B Cell Maturation

scholarly journals The Carbohydrate Lectin Receptor Dectin-1 Mediates the Immune Response to Exserohilum rostratum

2016 ◽  
Vol 85 (3) ◽  
Author(s):  
Jennifer L. Reedy ◽  
Paige E. Negoro ◽  
Marianela Feliu ◽  
Allison K. Lord ◽  
Nida S. Khan ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune Cell ◽  
Wide Spectrum ◽  
Granulomatous Inflammation ◽  
Necrosis Factor Alpha ◽  
Content Type ◽  
Macrophage Response ◽  
Lectin Receptor ◽  
Exserohilum Rostratum

ABSTRACT Dematiaceous molds are found ubiquitously in the environment and cause a wide spectrum of human disease, including infections associated with high rates of mortality. Despite this, the mechanism of the innate immune response has been less well studied, although it is key in the clearance of fungal pathogens. Here, we focus on Exserohilum rostratum, a dematiaceous mold that caused 753 infections during a multistate outbreak due to injection of contaminated methylprednisolone. We show that macrophages are incapable of phagocytosing Exserohilum. Despite a lack of phagocytosis, macrophage production of tumor necrosis factor alpha is triggered by hyphae but not spores and depends upon Dectin-1, a C-type lectin receptor. Dectin-1 is specifically recruited to the macrophage-hyphal interface but not the macrophage-spore interface due to differences in carbohydrate antigen expression between these two fungal forms. Corticosteroid and antifungal therapy perturb this response, resulting in decreased cytokine production. In vivo soft tissue infection in wild-type mice demonstrated that Exserohilum provokes robust neutrophilic and granulomatous inflammation capable of thwarting fungal growth. However, coadministration of methylprednisolone acetate results in robust hyphal tissue invasion and a significant reduction in immune cell recruitment. Our results suggest that Dectin-1 is crucial for macrophage recognition and the macrophage response to Exserohilum and that corticosteroids potently attenuate the immune response to this pathogen.

scholarly journals Systemic Expression of Notch Ligand Delta-Like 4 during Mycobacterial Infection Alters the T Cell Immune Response

2016 ◽  
Vol 7 ◽  
Author(s):  
Matthew A. Schaller ◽  
Ronald M. Allen ◽  
Soichiro Kimura ◽  
Cheryl L. Day ◽  
Steven L. Kunkel
Keyword(s):  
Immune Response ◽  
T Cell ◽  
Mycobacterial Infection ◽  
Cell Immune Response ◽  
Notch Ligand
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