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Cited by 240Immune Response and InflammationImmunotherapy and Immune ResponsesImmune responses and vaccinations

The DOI matches its Crossref record; 204 of the 205 references it cites were found in a registry or an index.

Sweeten PAMPs: role of sugar complexed PAMPs in innate immunity and vaccine biology

Open access
Mahla, Ranjeet Singh·2013·Frontiers in Immunology
DOI 10.3389/fimmu.2013.00248PMC PMC3759294
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Abstract

Innate sensors play a critical role in the early innate immune responses to invading pathogens through sensing of diverse biochemical signatures also known as pathogen associated molecular patterns (PAMPs). These biochemical signatures primarily consist of a major family of biomolecules such as proteins, lipids, nitrogen bases, and sugar and its complexes, which are distinct from host molecules and exclusively expressed in pathogens and essential to their survival. The family of sensors known as pattern recognition receptors (PRRs) are germ-line encoded, evolutionarily conserved molecules, and consist of Toll-like receptors (TLRs), RIG-I-like receptors (RLRs), NOD-like receptors (NLRs), C-type lectin-like receptors (CLRs), and DNA sensors. Sensing of PAMP by PRR initiates the cascade of signaling leading to the activation of transcription factors, such as NF-κB and interferon regulatory factors (IRFs), resulting in a variety of cellular responses, including the production of interferons (IFNs) and pro-inflammatory cytokines. In this review, we discuss sensing of different types of glycosylated PAMPs such as β-glucan (a polymeric sugar) or lipopolysaccharides, nucleic acid, and so on (sugar complex PAMPs) by different families of sensors, its role in pathogenesis, and its application in development of potential vaccine and vaccine adjuvants.

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Crossref · 10.3389/fimmu.2013.00248

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Figure 1 Sensing of SCPs through membrane associated PRRs, TLRs, and CLRs. In macrophages and dendritic cells plasma membrane localized TLRs (TLR1, TLR2, TLR4, and TLR6) and endosomal localized TLRs (TLR3, TLR7, TLR8, and TLR9) and TLR13 sense various SCPs as homo or heterodimer (shown in Table 1). TLR recruits MyD88, TRIFs, TIRAP, and TRAM adaptors for induction of inflammatory cytokines and type-I IFNs through activation of NF-κB and IRFs (IRF3 and IRF7) via IKKα/β and TBK1/IKK1, respectively. Dectin-1, Dectin-2, Mincle, and MCL are representative CLRs of Dectin-1 and Dectin-2 clusters. Sensing of various SCPs by Dectin-1 and Dectin-2 (shown in Table 1) recruits, Syk adaptor which further recruits PLCγ and activate cascade of signaling for induction of inflammatory cytokines via NF-κB and MAP kinases.
Figure 1 Sensing of SCPs through membrane associated PRRs, TLRs, and CLRs. In macrophages and dendritic cells plasma membrane localized TLRs (TLR1, TLR2, TLR4, and TLR6) and endosomal localized TLRs (TLR3, TLR7, TLR8, and TLR9) and TLR13 sense various SCPs as homo or heterodimer (shown in Table 1). TLR recruits MyD88, TRIFs, TIRAP, and TRAM adaptors for induction of inflammatory cytokines and type-I IFNs through activation of NF-κB and IRFs (IRF3 and IRF7) via IKKα/β and TBK1/IKK1, respectively. Dectin-1, Dectin-2, Mincle, and MCL are representative CLRs of Dectin-1 and Dectin-2 clusters. Sensing of various SCPs by Dectin-1 and Dectin-2 (shown in Table 1) recruits, Syk adaptor which further recruits PLCγ and activate cascade of signaling for induction of inflammatory cytokines via NF-κB and MAP kinases.CC BY · PubMed Central
Figure 2 Sensing of SCPs through cytosolic PRRs, RLRs, NLRs, and cytosolic DNA sensors. RLRs family member, RIG-I and MDA5 sense viral dsRNA (shown in Table 2), recruits an adaptor IPS-1 for induction of type-I IFNs and inflammatory cytokines. STING, a molecule plays a pivotal role in sensing of RNA. Several DNA sensors induce inflammatory cytokine and type-I IFNs in STING dependent and independent manner. NLRs family member, NOD1, NOD2, and inflammasome (mainly NLRP1 and NLRP3 and AIM2) induces inflammatory cytokine. NOD1 and NOD2 sense various SCPs (shown in Table 2) recruit an adaptor RIP2 and CARD9 for induction of inflammatory cytokines. Activation of inflammasome complex after stimulation with appropriate SCPs (shown in Table 2) process an inactive, proIL-1 family cytokine to active IL-1 family cytokine.
Figure 2 Sensing of SCPs through cytosolic PRRs, RLRs, NLRs, and cytosolic DNA sensors. RLRs family member, RIG-I and MDA5 sense viral dsRNA (shown in Table 2), recruits an adaptor IPS-1 for induction of type-I IFNs and inflammatory cytokines. STING, a molecule plays a pivotal role in sensing of RNA. Several DNA sensors induce inflammatory cytokine and type-I IFNs in STING dependent and independent manner. NLRs family member, NOD1, NOD2, and inflammasome (mainly NLRP1 and NLRP3 and AIM2) induces inflammatory cytokine. NOD1 and NOD2 sense various SCPs (shown in Table 2) recruit an adaptor RIP2 and CARD9 for induction of inflammatory cytokines. Activation of inflammasome complex after stimulation with appropriate SCPs (shown in Table 2) process an inactive, proIL-1 family cytokine to active IL-1 family cytokine.CC BY · PubMed Central
Figure 3 Role of SCPs in vaccine biology. Immunization of host (mice or human) with vaccine or vaccine adjuvant formulation PTC (PAMPs therapeutic complex) activates innate immune pathways (TLRs, CLRs, RLRs, NLRs, and DNA sensors), induce secretion of inflammatory cytokines and type-I IFNs. These cytokines further activate adaptive immune components through B and T lymphocytes. Adaptive immune memory cells protects host from infection.
Figure 3 Role of SCPs in vaccine biology. Immunization of host (mice or human) with vaccine or vaccine adjuvant formulation PTC (PAMPs therapeutic complex) activates innate immune pathways (TLRs, CLRs, RLRs, NLRs, and DNA sensors), induce secretion of inflammatory cytokines and type-I IFNs. These cytokines further activate adaptive immune components through B and T lymphocytes. Adaptive immune memory cells protects host from infection.CC BY · PubMed Central

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Metadata

Authors
Mahla, R. S.
Affiliations
Indian Institute of Science Education and Research, Bhopal (IN)
Corresponding author
Mahla, Ranjeet Singh
ORCID
Mahla, Ranjeet Singh
Venue
Frontiers in Immunology
Publisher
Frontiers Media SA
Published
2013
Volume
4
Pages
248-248
ISSN
1664-3224 (ISSN-L)
DOI
10.3389/fimmu.2013.00248
PMC
PMC3759294
OpenAlex
W2045475619
Cited by
239
References
205
Citations by year
2026: 4 · 2025: 11 · 2024: 23 · 2023: 20 · 2022: 26 · 2021: 34 · 2020: 34 · 2019: 34 · 2018: 19 · 2017: 19 · 2016: 7 · 2015: 3 · 2014: 4 · 2013: 1
FWCI
0.44
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Frontiers in Immunology (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Department of Biotechnology, Ministry of Science and Technology, India (SR/S2/RJN-55/2009, BT/PR6009/GBD/27/382/2012)
  • Department of Science and Technology, Ministry of Science and Technology, India
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
  • Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
  • Life Sciences › Immunology and Microbiology › Immunology › Immune responses and vaccinations
Keywords
pathogen-associated molecular patterns, innate immunity, pattern recognition receptors, Toll-like receptors, RIG-I-like receptors, NOD-like receptors, C-type lectin-like receptors, DNA biosensor, β-glucan, lipopolysaccharide, vaccine adjuvants, vaccine development, interferon signaling, NF-κB, inflammatory cytokines

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