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Sialic acids siglec interaction: a unique strategy to circumvent innate immune response by pathogens.

Khatua B, Roy S, Mandal C - Indian J. Med. Res. (2013)

Bottom Line: They promote association with the immune cells through sialic acids-siglec dependent manner.Such an association plays an important role to subvert host's immunity.Particular attention has been focused on Pseudomonas aeruginosa (PA) and Leishmania donovani.

View Article: PubMed Central - PubMed

Affiliation: Cancer Biology & Inflammatory Disorder Division, CSIR-Indian Institute of Chemical Biology, Kolkata, India.

ABSTRACT
Sialic acids (Sias) are nine-carbon keto sugars primarily present on the terminal residue of cell surface glycans. Sialic acid binding immunoglobulins (Ig)-like lectins (siglecs) are generally expressed on various immune cells. They selectively recognize different linkage-specific sialic acids and undertake a variety of cellular functions. Many pathogens either synthesize or acquire sialic acids from the host. Sialylated pathogens generally use siglecs to manipulate the host immune response. The present review mainly deals with the newly developed information regarding mechanism of acquisition of sialic acids by pathogens and their biological relevance especially in the establishment of successful infection by impairing host innate immunity. The pathogens which are unable to synthesize sialic acids might adsorb these from the host as a way to engage the inhibitory siglecs. They promote association with the immune cells through sialic acids-siglec dependent manner. Such an association plays an important role to subvert host's immunity. Detailed investigation of these pathways has been discussed in this review. Particular attention has been focused on Pseudomonas aeruginosa (PA) and Leishmania donovani.

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Related in: MedlinePlus

Schematic diagram of the proposed pathway of CD33 siglec-mediated suppression of cellular function in Leishmania infection. On macrophage, after ligand (present on various pathogen surface) binding with CD33 related siglecs, immunoreceptor tyrosine-based inhibition motif (ITIM) present on the cytosolic portion of siglecs get activated by phosphorylation with SH2 family kinases (Lyn, Syk). Then Src homology 2 domain-containing phosphatases 1 and 2 (SHP1 and SHP2) bind with the ITIM and get activated. These activated SHPs further dephosphorylate various signaling molecules and suppress cellular activation. The target of SHPs might be p38 mitogen-activated protein kinases (p38 MAPK) or Akt or nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kβ) and ultimately downregulate the effector functions of the cell. In macrophages this siglec-mediated pathway might regulate the polarization of macrophage function towards anti-inflammatory type by reducing Th1 cytokines (IFNγ) and increasing Th2 cytokines (IL-10) along with downregulating inducible nitric oxide synthase (iNOS) gene expression for nitric oxide (NO) secretion.
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Figure 5: Schematic diagram of the proposed pathway of CD33 siglec-mediated suppression of cellular function in Leishmania infection. On macrophage, after ligand (present on various pathogen surface) binding with CD33 related siglecs, immunoreceptor tyrosine-based inhibition motif (ITIM) present on the cytosolic portion of siglecs get activated by phosphorylation with SH2 family kinases (Lyn, Syk). Then Src homology 2 domain-containing phosphatases 1 and 2 (SHP1 and SHP2) bind with the ITIM and get activated. These activated SHPs further dephosphorylate various signaling molecules and suppress cellular activation. The target of SHPs might be p38 mitogen-activated protein kinases (p38 MAPK) or Akt or nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kβ) and ultimately downregulate the effector functions of the cell. In macrophages this siglec-mediated pathway might regulate the polarization of macrophage function towards anti-inflammatory type by reducing Th1 cytokines (IFNγ) and increasing Th2 cytokines (IL-10) along with downregulating inducible nitric oxide synthase (iNOS) gene expression for nitric oxide (NO) secretion.

Mentions: We further try to investigate whether sialic acids-siglec interaction modulate the immune response during leishmania infection. Preliminary findings reveal the phosphatase-mediated deactivation of various signaling pathways is differentially regulated in presence or absence of sialic acids-siglec interaction (Fig. 5, unpublished data).


Sialic acids siglec interaction: a unique strategy to circumvent innate immune response by pathogens.

Khatua B, Roy S, Mandal C - Indian J. Med. Res. (2013)

Schematic diagram of the proposed pathway of CD33 siglec-mediated suppression of cellular function in Leishmania infection. On macrophage, after ligand (present on various pathogen surface) binding with CD33 related siglecs, immunoreceptor tyrosine-based inhibition motif (ITIM) present on the cytosolic portion of siglecs get activated by phosphorylation with SH2 family kinases (Lyn, Syk). Then Src homology 2 domain-containing phosphatases 1 and 2 (SHP1 and SHP2) bind with the ITIM and get activated. These activated SHPs further dephosphorylate various signaling molecules and suppress cellular activation. The target of SHPs might be p38 mitogen-activated protein kinases (p38 MAPK) or Akt or nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kβ) and ultimately downregulate the effector functions of the cell. In macrophages this siglec-mediated pathway might regulate the polarization of macrophage function towards anti-inflammatory type by reducing Th1 cytokines (IFNγ) and increasing Th2 cytokines (IL-10) along with downregulating inducible nitric oxide synthase (iNOS) gene expression for nitric oxide (NO) secretion.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3928697&req=5

Figure 5: Schematic diagram of the proposed pathway of CD33 siglec-mediated suppression of cellular function in Leishmania infection. On macrophage, after ligand (present on various pathogen surface) binding with CD33 related siglecs, immunoreceptor tyrosine-based inhibition motif (ITIM) present on the cytosolic portion of siglecs get activated by phosphorylation with SH2 family kinases (Lyn, Syk). Then Src homology 2 domain-containing phosphatases 1 and 2 (SHP1 and SHP2) bind with the ITIM and get activated. These activated SHPs further dephosphorylate various signaling molecules and suppress cellular activation. The target of SHPs might be p38 mitogen-activated protein kinases (p38 MAPK) or Akt or nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kβ) and ultimately downregulate the effector functions of the cell. In macrophages this siglec-mediated pathway might regulate the polarization of macrophage function towards anti-inflammatory type by reducing Th1 cytokines (IFNγ) and increasing Th2 cytokines (IL-10) along with downregulating inducible nitric oxide synthase (iNOS) gene expression for nitric oxide (NO) secretion.
Mentions: We further try to investigate whether sialic acids-siglec interaction modulate the immune response during leishmania infection. Preliminary findings reveal the phosphatase-mediated deactivation of various signaling pathways is differentially regulated in presence or absence of sialic acids-siglec interaction (Fig. 5, unpublished data).

Bottom Line: They promote association with the immune cells through sialic acids-siglec dependent manner.Such an association plays an important role to subvert host's immunity.Particular attention has been focused on Pseudomonas aeruginosa (PA) and Leishmania donovani.

View Article: PubMed Central - PubMed

Affiliation: Cancer Biology & Inflammatory Disorder Division, CSIR-Indian Institute of Chemical Biology, Kolkata, India.

ABSTRACT
Sialic acids (Sias) are nine-carbon keto sugars primarily present on the terminal residue of cell surface glycans. Sialic acid binding immunoglobulins (Ig)-like lectins (siglecs) are generally expressed on various immune cells. They selectively recognize different linkage-specific sialic acids and undertake a variety of cellular functions. Many pathogens either synthesize or acquire sialic acids from the host. Sialylated pathogens generally use siglecs to manipulate the host immune response. The present review mainly deals with the newly developed information regarding mechanism of acquisition of sialic acids by pathogens and their biological relevance especially in the establishment of successful infection by impairing host innate immunity. The pathogens which are unable to synthesize sialic acids might adsorb these from the host as a way to engage the inhibitory siglecs. They promote association with the immune cells through sialic acids-siglec dependent manner. Such an association plays an important role to subvert host's immunity. Detailed investigation of these pathways has been discussed in this review. Particular attention has been focused on Pseudomonas aeruginosa (PA) and Leishmania donovani.

Show MeSH
Related in: MedlinePlus