Omp25‐dependent engagement of SLAMF1 by Brucella abortus in dendritic cells limits acute inflammation and favours bacterial persistence in vivo

The strategies by which intracellular pathogenic bacteria manipulate innate immunity to establish chronicity are poorly understood. Here, we show that Brucella abortus outer membrane protein Omp25 specifically binds the immune cell receptor SLAMF1 in vitro. The Omp25‐dependent engagement of SLAMF1 by B. abortus limits NF‐κB translocation in dendritic cells (DCs) with no impact on Brucella intracellular trafficking and replication. This in turn decreases pro‐inflammatory cytokine secretion and impairs DC activation. The Omp25‐SLAMF1 axis also dampens the immune response without affecting bacterial replication in vivo during the acute phase of Brucella infection in a mouse model. In contrast, at the chronic stage of infection, the Omp25/SLAMF1 engagement is essential for Brucella persistence. Interaction of a specific bacterial protein with an immune cell receptor expressed on the DC surface at the acute stage of infection is thus a powerful mechanism to support microbe settling in its replicative niche and progression to chronicity.

[1]  C. Alfonso‐Rodríguez,et al.  Biomaterials Used for Periodontal Disease Treatment: Focusing on Immunomodulatory Properties , 2022, International journal of biomaterials.

[2]  E. J. Young.  Clinical Manifestations of Human Brucellosis , 2020 .

[3]  G. Victora,et al.  Studying interactions between dendritic cells and T cells in vivo. , 2019, Current opinion in immunology.

[4]  L. Donis-Maturano,et al.  Dendritic cells and Brucella spp. interaction: the sentinel host and the stealthy pathogen , 2019, Folia Microbiologica.

[5]  B. Malissen,et al.  Novel Cre-Expressing Mouse Strains Permitting to Selectively Track and Edit Type 1 Conventional Dendritic Cells Facilitate Disentangling Their Complexity in vivo , 2018, Front. Immunol..

[6]  E. Moreno,et al.  Persistence of Brucella abortus in the Bone Marrow of Infected Mice , 2018, Journal of immunology research.

[7]  M. Yurchenko,et al.  SLAMF1 is required for TLR4-mediated TRAM-TRIF–dependent signaling in human macrophages , 2018, The Journal of cell biology.

[8]  M. Naassila,et al.  Signaling lymphocytic activation molecules Slam and cancers: friends or foes? , 2018, Oncotarget.

[9]  C. Buchrieser,et al.  The Life Cycle of L. pneumophila: Cellular Differentiation Is Linked to Virulence and Metabolism , 2018, Front. Cell. Infect. Microbiol..

[10]  J. Gorvel,et al.  Immunomodulatory properties of Brucella melitensis lipopolysaccharide determinants on mouse dendritic cells in vitro and in vivo , 2017, Virulence.

[11]  F. Tuon,et al.  Human‐to‐human transmission of Brucella – a systematic review , 2017, Tropical medicine & international health : TM & IH.

[12]  R. Tsolis,et al.  Chronic Bacterial Pathogens: Mechanisms of Persistence , 2016, Microbiology spectrum.

[13]  R. Tsolis,et al.  Brucella spp. Virulence Factors and Immunity. , 2016, Annual review of animal biosciences.

[14]  P. Engel,et al.  Responses to Microbial Challenges by SLAMF Receptors , 2016, Front. Immunol..

[15]  J. Gorvel,et al.  Brucella discriminates between mouse dendritic cell subsets upon in vitro infection , 2015, Virulence.

[16]  J. Gorvel,et al.  Subversion of mouse dendritic cell subset function by bacterial pathogens. , 2015, Microbial pathogenesis.

[17]  Michael Poidinger,et al.  Identification of cDC1- and cDC2-committed DC progenitors reveals early lineage priming at the common DC progenitor stage in the bone marrow , 2015, Nature Immunology.

[18]  R. Banchereau,et al.  Brucella CβG induces a dual pro- and anti-inflammatory response leading to a transient neutrophil recruitment , 2015, Virulence.

[19]  E. Moreno.  Retrospective and prospective perspectives on zoonotic brucellosis , 2014, Front. Microbiol..

[20]  H. Lepidi,et al.  BtpB, a novel Brucella TIR-containing effector protein with immune modulatory functions , 2013, Front. Cell. Infect. Microbiol..

[21]  S. Morrison,et al.  SLAM family markers resolve functionally distinct subpopulations of hematopoietic stem cells and multipotent progenitors. , 2013, Cell stem cell.

[22]  R. Bhatnagar,et al.  Cell mediated immune response after challenge in Omp25 liposome immunized mice contributes to protection against virulent Brucella abortus 544. , 2013, Vaccine.

[23]  E. Schelling,et al.  Clinical Manifestations of Human Brucellosis: A Systematic Review and Meta-Analysis , 2012, PLoS neglected tropical diseases.

[24]  E. Klechevsky,et al.  Brucella β 1,2 Cyclic Glucan Is an Activator of Human and Mouse Dendritic Cells , 2012, PLoS pathogens.

[25]  M. Fresno,et al.  The Receptor Slamf1 on the Surface of Myeloid Lineage Cells Controls Susceptibility to Infection by Trypanosoma cruzi , 2012, PLoS pathogens.

[26]  R. Bhatnagar,et al.  Intradermal immunization with outer membrane protein 25 protects Balb/c mice from virulent B. abortus 544. , 2012, Molecular immunology.

[27]  J. Gorvel,et al.  Internal affairs: investigating the Brucella intracellular lifestyle. , 2012, FEMS microbiology reviews.

[28]  Anna R Martirosyan,et al.  The Lipopolysaccharide Core of Brucella abortus Acts as a Shield Against Innate Immunity Recognition , 2012, PLoS pathogens.

[29]  E. Moreno,et al.  What have we learned from brucellosis in the mouse model? , 2012, Veterinary Research.

[30]  Guoxing Wang,et al.  Receptor Signaling Lymphocyte-activation Molecule Family 1 (Slamf1) Regulates Membrane Fusion and NADPH Oxidase 2 (NOX2) Activity by Recruiting a Beclin-1/Vps34/Ultraviolet Radiation Resistance-associated Gene (UVRAG) Complex* , 2012, The Journal of Biological Chemistry.

[31]  Fernanda S. Oliveira,et al.  Host Susceptibility to Brucella abortus Infection Is More Pronounced in IFN-γ knockout than IL-12/β2-Microglobulin Double-Deficient Mice , 2011, Clinical & developmental immunology.

[32]  S. Tangye,et al.  SLAM family receptors and SAP adaptors in immunity. , 2011, Annual review of immunology.

[33]  Anna R Martirosyan,et al.  An evolutionary strategy for a stealthy intracellular Brucella pathogen , 2011, Immunological reviews.

[34]  G. Pappas,et al.  Cell-mediated immunity in human brucellosis. , 2011, Microbes and infection.

[35]  M. Boes,et al.  SLAM is a microbial sensor that regulates bacterial phagosome functions in macrophages , 2010, Nature Immunology.

[36]  B. Wren,et al.  Liposomal delivery of p-ialB and p-omp25 DNA vaccines improves immunogenicity but fails to provide full protection against B. melitensis challenge , 2010, Genetic vaccines and therapy.

[37]  J. Gorvel,et al.  Transcriptome Analysis of the Brucella abortus BvrR/BvrS Two-Component Regulatory System , 2010, PloS one.

[38]  G. Tsokos,et al.  SLAM family receptors and the SLAM-associated protein (SAP) modulate T cell functions , 2010, Seminars in Immunopathology.

[39]  A. Cloeckaert,et al.  Analysis of the occurrence and distribution of the Omp25/Omp31 family of surface proteins in the six classical Brucella species. , 2009, Veterinary microbiology.

[40]  R. Medzhitov,et al.  Targeting of immune signalling networks by bacterial pathogens , 2009, Nature Cell Biology.

[41]  S. Estein,et al.  Immunization with Recombinant Brucella Species Outer Membrane Protein Omp16 or Omp19 in Adjuvant Induces Specific CD4+ and CD8+ T Cells as Well as Systemic and Oral Protection against Brucella abortus Infection , 2008, Infection and Immunity.

[42]  R. Ugalde,et al.  Brucella Control of Dendritic Cell Maturation Is Dependent on the TIR-Containing Protein Btp1 , 2008, PLoS pathogens.

[43]  R. Gazzinelli,et al.  Central Role of MyD88-Dependent Dendritic Cell Maturation and Proinflammatory Cytokine Production to Control Brucella abortus Infection1 , 2008, The Journal of Immunology.

[44]  C. Guzmán-Verri,et al.  BvrR/BvrS-Controlled Outer Membrane Proteins Omp3a and Omp3b Are Not Essential for Brucella abortus Virulence , 2007, Infection and Immunity.

[45]  A. Gross,et al.  Brucella suis Prevents Human Dendritic Cell Maturation and Antigen Presentation through Regulation of Tumor Necrosis Factor Alpha Secretion , 2007, Infection and Immunity.

[46]  P. De Baetselier,et al.  MyD88-Dependent Activation of B220−CD11b+LY-6C+ Dendritic Cells during Brucella melitensis Infection1 , 2007, The Journal of Immunology.

[47]  P. Sansonetti,et al.  Debugging how bacteria manipulate the immune response. , 2007, Immunity.

[48]  B. Wren,et al.  The identification of two protective DNA vaccines from a panel of five plasmid constructs encoding Brucella melitensis 16M genes. , 2007, Vaccine.

[49]  E. Rajnavölgyi,et al.  SLAM/SLAM interactions inhibit CD40-induced production of inflammatory cytokines in monocyte-derived dendritic cells. , 2006, Blood.

[50]  A. Gross,et al.  High Susceptibility of Human Dendritic Cells to Invasion by the Intracellular Pathogens Brucella suis, B. abortus, and B. melitensis , 2005, Infection and Immunity.

[51]  N. Commander,et al.  Brucellosis – new aspects of an old disease , 2005, Journal of applied microbiology.

[52]  Hao Wang,et al.  Genetic evidence linking SAP, the X-linked lymphoproliferative gene product, to Src-related kinase FynT in T(H)2 cytokine regulation. , 2004, Immunity.

[53]  V. García,et al.  Expression of Signaling Lymphocytic Activation Molecule- Associated Protein Interrupts IFN-γ Production in Human Tuberculosis 1 , 2004, The Journal of Immunology.

[54]  E. Moreno,et al.  Brucella intracellular life: from invasion to intracellular replication. , 2002, Veterinary microbiology.

[55]  P. Elzer,et al.  Brucella species lacking the major outer membrane protein Omp25 are attenuated in mice and protect against Brucella melitensis and Brucella ovis. , 2002, Veterinary microbiology.

[56]  B. Robinson-Dunn.  The microbiology laboratory's role in response to bioterrorism. , 2002, Archives of pathology & laboratory medicine.

[57]  G. Cheng,et al.  Signaling Lymphocytic Activation Molecule Is Expressed on CD40 Ligand-Activated Dendritic Cells and Directly Augments Production of Inflammatory Cytokines1 , 2001, The Journal of Immunology.

[58]  M. Álvarez-Martínez,et al.  Major Outer Membrane Protein Omp25 of Brucella suis Is Involved in Inhibition of Tumor Necrosis Factor Alpha Production during Infection of Human Macrophages , 2001, Infection and Immunity.

[59]  D. Sánchez,et al.  A Homologue of an Operon Required for DNA Transfer in Agrobacterium Is Required in Brucella abortusfor Virulence and Intracellular Multiplication , 2000, Journal of bacteriology.

[60]  E. M. Hoffmann,et al.  Mechanism of serum resistance among Brucella abortus isolates. , 1999, Veterinary microbiology.

[61]  M. J. Corbel,et al.  Brucellosis: an overview. , 1997, Emerging infectious diseases.

[62]  A. Cloeckaert,et al.  Nucleotide sequence and expression of the gene encoding the major 25-kilodalton outer membrane protein of Brucella ovis: Evidence for antigenic shift, compared with other Brucella species, due to a deletion in the gene , 1996, Infection and immunity.

[63]  B. Cocks,et al.  A novel receptor involved in T-cell activation , 1995, Nature.

[64]  P. de Wergifosse,et al.  Cloning and nucleotide sequence of the gene coding for the major 25-kilodalton outer membrane protein of Brucella abortus , 1995, Journal of bacteriology.

[65]  P. de Wergifosse,et al.  Demonstration of peptidoglycan-associated Brucella outer-membrane proteins by use of monoclonal antibodies. , 1992, Journal of General Microbiology.

[66]  K. Kelly,et al.  SDS-soluble and peptidoglycan-bound proteins in the outer membrane-peptidoglycan complex of Brucella abortus. , 1991, Veterinary microbiology.

[67]  S. Slavin,et al.  TRANSMISSION OF BRUCELLOSIS BY BONE MARROW TRANSPLANTATION , 1982, The Lancet.