title: Induction of Mincle by Helicobacter pylori and consequent anti-inflammatory signaling denote a bacterial survival strategy.
abstract: Evasion of innate immune recognition is one of the key strategies for persistence of Helicobacter pylori, by virtue of its ability to modulate or escape the host innate immune receptors and signaling pathways. C-type lectin receptors (CLRs) predominantly expressed by macrophages are pivotal in tailoring immune response against pathogens. The recognition of glyco or carbohydrate moieties by Mincle (Macrophage inducible C-type lectin) is emerging as a crucial element in anti-fungal and anti-mycobacterial immunity. Herein, we demonstrate the role of Mincle in modulation of innate immune response against H. pylori infection. Our results revealed an upregulated expression of Mincle which was independent of direct host cell contact. Upon computational modelling, Mincle was observed to interact with the Lewis antigens of H. pylori LPS and possibly activating an anti-inflammatory cytokine production, thereby maintaining a balance between pro- and anti-inflammatory cytokine production. Furthermore, siRNA mediated knockdown of Mincle in human macrophages resulted in up regulation of pro-inflammatory cytokines and consequent down regulation of anti-inflammatory cytokines. Collectively, our study demonstrates a novel mechanism employed by H. pylori to escape clearance by exploiting functional plasticity of Mincle to strike a balance between pro-and anti-inflammatory responses ensuring its persistence in the host.
authors.affiliation: Pathogen Biology Laboratory, Department of Biotechnology and Bioinformatics, University of Hyderabad, Hyderabad, Telangana, India.
authors.forename: Savita
authors.initials: S
authors.lastname: Devi
authors.affiliation: Department of Biotechnology, Indian Institute of Technology Hyderabad, Yeddumailaram, Telangana, India.
authors.forename: Eerappa
authors.initials: E
authors.lastname: Rajakumara
authors.affiliation: Pathogen Biology Laboratory, Department of Biotechnology and Bioinformatics, University of Hyderabad, Hyderabad, Telangana, India.
authors.forename: Niyaz
authors.initials: N
authors.lastname: Ahmed
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D002460:Cell Line; D005786:Gene Expression Regulation; D016480:Helicobacter pylori / Q000276:immunology*; D006801:Humans; D057131:Immune Evasion; D016753:Interleukin-10 / Q000096:biosynthesis / Q000276:immunology; D037181:Lectins, C-Type / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology*; D008070:Lipopolysaccharides / Q000737:chemistry / Q000276:immunology*; D008262:Macrophage Activation; D008264:Macrophages / Q000276:immunology / Q000382:microbiology*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D011971:Receptors, Immunologic / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology*; D016415:Sequence Alignment; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000276:immunology
chemical_list: C482593:CLEC4D protein, human; C508609:IL10 protein, human; D037181:Lectins, C-Type; D008070:Lipopolysaccharides; D034741:RNA, Small Interfering; D011971:Receptors, Immunologic; D014409:Tumor Necrosis Factor-alpha; C442865:lipopolysaccharide, Helicobacter pylori; D016753:Interleukin-10