Surface immunogenic protein from Streptococcus agalactiae and Fissurella latimarginata hemocyanin are TLR4 ligands and activate MyD88- and TRIF dependent signaling pathways

نویسندگان

چکیده

The development of vaccine adjuvants is interest for the management chronic diseases, cancer, and future pandemics. Therefore, role Toll-like receptors (TLRs) in effects has been investigated. TLR4 ligand-based are most frequently used human vaccines. Among TLR family members, unique dual signaling capabilities due to recruitment two adapter proteins, myeloid differentiation marker 88 (MyD88) interferon-β inducer containing toll-interleukin-1 receptor (TIR) domain (TRIF). MyD88-mediated triggers a proinflammatory innate immune response, while TRIF-mediated leads an adaptive response. Most studies have lipopolysaccharide-based ligands as adjuvants; however, although protein-based proven advantageous adjuvants, their mechanisms action, including ability undergo structural modifications achieve optimal immunogenicity, explored less thoroughly. In this work, we characterized (PBAs) on via MyD88 TRIF. As models TLR4-PBAs, hemocyanin from Fissurella latimarginata (FLH) recombinant surface immunogenic protein (rSIP) Streptococcus agalactiae . We determined that rSIP FLH partial agonists, depending agonist used, bias toward TRIF or pathway. Furthermore, when characterizing gene products with pathway-dependent expression, differences TLR4-associated were observed. require activate nuclear factor kappa beta (NF-κB) interferon regulatory (IRF). However, specific pattern interleukin 6 (IL-6) gamma-induced 10 (IP-10) secretion associated recruitment. Functionally, promote antigen cross-presentation manner dependent TLR4, signaling. activates TRIF-dependent pathway cytokine expression cross-presentation. Finally, work supports use these TLR4-PBAs clinically useful selectively TRIF- MyD88-dependent drive safe responses vigorous Th1 responses.

برای دانلود باید عضویت طلایی داشته باشید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Distinct single-cell signaling characteristics are conferred by the MyD88 and TRIF pathways during TLR4 activation.

Toll-like receptors (TLRs) recognize specific pathogen-associated molecular patterns and initiate innate immune responses through signaling pathways that depend on the adaptor proteins MyD88 (myeloid differentiation marker 88) or TRIF (TIR domain-containing adaptor protein-inducing interferon-β). TLR4, in particular, uses both adaptor proteins to activate the transcription factor nuclear factor...

متن کامل

TLR2 and TLR4 Signaling Pathways and Gastric Cancer: Insights from Transcriptomics and Sample Validation

Background: Pattern recognition receptors, especially toll-like receptors (TLRs), as the first line of defense for pathogen detection, were found to be associated with H.­ pylori infection and gastric cancer (GC). However, the expression levels of TLRs, i.e. TLR2 and TLR4, as the main receptors sensed by H.­ pylori, still remain largely ambiguous. We aimed to investigate the patterns of key tra...

متن کامل

A Novel Immunomodulatory Hemocyanin from the Limpet Fissurella latimarginata Promotes Potent Anti-Tumor Activity in Melanoma

Hemocyanins, the huge oxygen-transporting glycoproteins of some mollusks, are used as immunomodulatory proteins with proven anti-cancer properties. The biodiversity of hemocyanins has promoted interest in identifying new anti-cancer candidates with improved immunological properties. Hemocyanins promote Th1 responses without known side effects, which make them ideal for long-term sustained treat...

متن کامل

Beyond MyD88 and TRIF Pathways in Toll-Like Receptor Signaling

The Toll-like receptors (TLRs), 13 types known to-date, are a major class of transmembrane proteins of the mammalian innate immune system (1). They are known to detect diverse pathogen-associated molecular patterns of microorganisms, and trigger specialized sets of signal transduction cascades that neutralize any danger posed to the host by the intruders. The major adaptors that bind to the int...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

ژورنال

عنوان ژورنال: Frontiers in Immunology

سال: 2023

ISSN: ['1664-3224']

DOI: https://doi.org/10.3389/fimmu.2023.1186188