Fucosyltransferase IV and VII-directed selectin ligand function determines long-term survival in experimental tuberculosis

Ehlers, Stefan; Schreiber, Tanja; Dunzendorfer, Annette; Lowe, John B.; Hölscher, Christoph

doi:10.1016/j.imbio.2008.12.009

Cited by 8 publications

(11 citation statements)

References 27 publications

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“…Interestingly, FtDKO mice exhibit similar kinetics of clearance of Mycobacterium tuberculosis and Lymphocytic choriomeningitis virus infections in visceral organs [19], [35], despite a disparate frequency of CD8 + T cells in the lymph node but similar frequencies in other organs [20], [35], [36]. In contrast, FtDKO mice had significantly decreased splenic burden of LM-OVA as early as 1 day after infection.…”

Section: Discussionmentioning

confidence: 95%

Lack of Functional Selectin Ligand Interactions Compromises Long Term Tumor Protection by CD8+ T Cells

et al. 2012

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Central memory CD8+ T cells expressing the adhesion molecule CD62L (L-selectin) are potent mediators of anti-cancer immunity due to their ability to proliferate extensively upon antigen re-stimulation. The interaction of selectin with its ligands mediates leukocyte rolling along high endothelial venules. Mice deficient in α(1,3) Fucosyltransferase IV and VII (FtDKO) lack functional L, P and E selectin ligands. Thus, we addressed whether the lack of selectin ligand interactions alters tumor protection by CD8+ T cells in FtDKO mice. Listeria monocytogenes-OVA (LM-OVA) infection evoked potent OVA-specific CD8+ T cells that proliferated and contracted at similar kinetics and phenotype in FtDKO and wild-type mice. Additionally, OVA-specific CD8+ T cells in both mouse strains exhibited similar phenotypic differentiation, in vivo cytolytic activity and IFN-γ expression. However, FtDKO mice succumbed to B16-OVA tumors significantly earlier than wild-type mice. In contrast, FtDKO mice evoked strong recall memory CD8+ T cell responses and protection to systemic LM-OVA re-challenge. The diminished tumor protection in FtDKO mice was not related to defective antigen presentation by dendritic cells or reduced proliferation of antigen-specific CD8+ T cells. However, WT or FtDKO OVA-specific CD8+ T cells showed significantly reduced ability to traffic to lymph nodes upon adoptive transfer into naïve FtDKO recipients. Furthermore, FtDKO OVA-specific CD8+ T cells displayed poor ability to infiltrate tumors growing in WT mice. These results reveal that selectin ligand expression on host endothelium as well CD8+ T cells may be important for their efficient and continued extravasation into peripheral tumors.

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Section: Discussionmentioning

confidence: 95%

Lack of Functional Selectin Ligand Interactions Compromises Long Term Tumor Protection by CD8+ T Cells

et al. 2012

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“…However, the possibility of infection‐induced hematopoiesis in extramedullary tissues, such as the spleen, cannot be ruled out . FucT‐IV and ‐VII expression has also been implicated in modulating host immunity to bacterial infections induced by Mycobacterium tuberculosis and Anaplasma phagocytophilum infections . Acute infection of FtDKO mice with low dose M. tuberculosis (∼100 CFUs per lung) leads to control of bacterial proliferation.…”

Section: Discussionmentioning

confidence: 99%

“…This is attributed to recruitment of activated T cells into the lungs similar to WT mice but delayed T cell and macrophage effector response . However, FtDKO mice with chronic M. tuberculosis infection exhibit decreased survival capability compared to WT controls despite similar bacterial growth and tissue pathology in infected organs . In contrast, the lack of FucT‐IV and ‐VII expression has been associated with decreased neutrophil binding of A. phagocytophilum , a neutrophil‐tropic bacterium .…”

Section: Discussionmentioning

confidence: 99%

“…26 FucT-IV and -VII expression has also been implicated in modulating host immunity to bacterial infections induced by Mycobacterium tuberculosis and Anaplasma phagocytophilum infections. [27][28][29] Acute infection of FtDKO mice with low dose M. tuberculosis (∼100 CFUs per lung) leads to control of bacterial proliferation. This is attributed to recruitment of activated T cells into the lungs similar to WT mice but delayed T cell and macrophage effector response.…”

Section: Discussionmentioning

confidence: 99%

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Lack of functional selectin-ligand interactions enhances innate immune resistance to systemic Listeria monocytogenes infection

Agbayani

Gurnani

Zafer

et al. 2017

Journal of Leukocyte Biology

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Selectin-ligand interactions are important for leukocyte homing and functionality. The roles of selectin-ligand interactions in modulating immunity to intracellular infections are not completely understood. Mice lacking the expression of fucosyltransferase-IV and -VII (Fucosyltransferase-IV and -VII double knockout, FtDKO) exhibit deficient functionality of selectin-ligand interactions. We addressed the kinetics of infection and immunity to Listeria monocytogenes (LM), an intracellular pathogen, in FtDKO mice. These mice exhibited enhanced ability to clear infection and increased survival to a lethal dose of LM infection relative to wild-type (WT) C57BL/6J controls. This was associated with increased levels of neutrophils, monocytes, and dendritic cells (DCs) in the blood and/or infected organs. Adoptive transfer of bone marrow (BM) cells from FtDKO mice to WT mice resulted in enhanced neutrophil numbers and improved clearance of LM bacteria in recipients. In vivo depletion of myeloid innate immune cells, particularly neutrophils, monocytes, macrophages, and DCs, using anti-Ly-6G (RB6-8C5) monoclonal antibody, reduced the ability of FtDKO mice to curtail LM infection. Nevertheless, depletion using anti-Ly-6G (1A8) known to exclusively deplete neutrophils did not abrogate increased resistance of FtDKO mice to LM infection, suggesting a role for other myeloid innate immune cells in this model. Examination of BM hematopoietic progenitors through flow cytometry and cell culture colony-forming unit assay showed increased frequencies of granulocyte-macrophage progenitors in FtDKO relative to WT mice, Overall, our results indicate that functional selectin ligand deficiency enhances innate immune-mediated resistance to systemic LM infection despite defective leukocyte migration and lymphocyte homing.

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“…Le x , Le y and Sialyl-Le x ), one of the major components of cell surface oligosaccharides. One of them, Sialyl-Le x , is involved, due to its external position, in numerous cell-cell interactions occurring during embryo implantation [1], malignant transformation [2] and inflammation [3]. …”

Section: Introductionmentioning

confidence: 99%

Characterization of bovine FUT7 furthers understanding of FUT7 evolution in mammals

et al. 2012

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BackgroundThe Sialyl-Lewis X (Slex) is a well-known glycan structure involved in leukocyte homing and recruitment to inflammatory sites. SLex is well conserved among species and is mainly synthesized by FucT-VII in vertebrates. The enzyme responsible for its biosynthesis in cattle was not known.ResultsWe cloned a cDNA sequence encoding bovine α3-fucosyltransferase VII that shares 83% identity with its human counterpart. Located at the BTA 11 telomeric region, the 1029 bp open reading frame is spread over two different exons, E1 which also contains the unique 5’-untranslated region and E2 which includes the entire 3’-untranslated region. The bfut7 expression pattern is restricted to thymus and spleen. A single transcript leading to the synthesis of a 342 aa protein was identified. The encoded fucosyltransferase, produced as a recombinant enzyme in COS-1 cells, was shown to be specifically responsible for SLex synthesis in cattle. In addition, we showed that the gene promoter evolved from fish to mammals towards a complex system related to the immune system. But beyond the fact that the gene regulation seems to be conserved among mammals, we also identified 7 SNPs including 3 missense mutations in the coding region in a small panel of animals.ConclusionsThe FUT7 sequence was highly conserved as well as the specific activity of the encoded protein FucT-VII. In addition, our in silico promoter analysis and the high rate of polymorphism suggested that its function is evolving toward a complex system related to the immune system. Furthermore, comparing bovine to human and mouse sequences, it appeared that a decrease in gene regulation was correlated with an increase in mutation rate and wider tissue expression.

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Fucosyltransferase IV and VII-directed selectin ligand function determines long-term survival in experimental tuberculosis

Cited by 8 publications

References 27 publications

Lack of Functional Selectin Ligand Interactions Compromises Long Term Tumor Protection by CD8+ T Cells

Lack of Functional Selectin Ligand Interactions Compromises Long Term Tumor Protection by CD8+ T Cells

Lack of functional selectin-ligand interactions enhances innate immune resistance to systemic Listeria monocytogenes infection

Characterization of bovine FUT7 furthers understanding of FUT7 evolution in mammals

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