Recognition of Coxiella burnetii by toll-like receptors and nucleotide-binding oligomerization domain-like receptors.

BACKGROUND Infection with Coxiella burnetii can lead to acute and chronic Q fever. Toll-like receptor 1 (TLR1), TLR2, TLR4, TLR6, nucleotide-binding oligomerization domain receptor 1 (NOD1), NOD2, and the mitogen-activated protein kinases are central in the innate immune response against microorganisms, but little is known about their role in the recognition of C. burnetii in humans. METHODS Human peripheral blood mononuclear cells (PBMCs) were stimulated with C. burnetii Nine Mile and the Dutch outbreak isolate C. burnetii 3262. TLRs were inhibited using specific antibodies or antagonists. Additionally, the influence of human polymorphisms in TLRs and Nod-like receptors (NLRs) on C. burnetii-induced cytokine production was assessed. RESULTS Inhibition of TLR2, p38, JNK, and ERK led to decreased cytokine responses in C. burnetii-stimulated human PBMCs. Humans with polymorphisms in TLR1 and NOD2 had reduced cytokine production, compared with humans with wild-type genotypes, after stimulation. Interestingly, polymorphisms in TLR6 led to decreased cytokine production after C. burnetii 3262 stimulation but not after C. burnetii Nine Mile stimulation. CONCLUSIONS The TLR1/TLR2 heterodimer and NOD2 are important recognition receptors for the induction of cytokine responses against C. burnetii in humans. Furthermore, an interesting finding was the divergent recognition of C. burnetii Nine Mile and C. burnetii 3262.

[1]  M. Oosting,et al.  TLR1, TLR2, and TLR6 gene polymorphisms are associated with increased susceptibility to complicated skin and skin structure infections. , 2014, The Journal of infectious diseases.

[2]  J. Oosterheert,et al.  Delayed Diagnosis of Chronic Q Fever and Cardiac Valve Surgery , 2013, Emerging infectious diseases.

[3]  T. Miyakawa,et al.  Genomic responses in mouse models poorly mimic human inflammatory diseases , 2013 .

[4]  Alexander Hoischen,et al.  Functional genomics identifies type I interferon pathway as central for host defense against Candida albicans , 2013, Nature Communications.

[5]  J. Rebel,et al.  Q Fever in Pregnant Goats: Pathogenesis and Excretion of Coxiella burnetii , 2012, PloS one.

[6]  M. Oosting,et al.  Toll-like receptor 1 polymorphisms increase susceptibility to candidemia. , 2012, The Journal of infectious diseases.

[7]  L. Joosten,et al.  Neisseria meningitidis lipid A mutant LPSs function as LPS antagonists in humans by inhibiting TLR 4-dependent cytokine production , 2011, Innate immunity.

[8]  F. V. van Zijderveld,et al.  Molecular Epidemiology of Coxiella burnetii from Ruminants in Q Fever Outbreak, the Netherlands , 2011, Emerging infectious diseases.

[9]  M. Oosting,et al.  Recognition of Borrelia burgdorferi by NOD2 is central for the induction of an inflammatory reaction. , 2010, The Journal of infectious diseases.

[10]  G. E. Etokebe,et al.  Toll‐Like Receptor 2 (P631H) Mutant Impairs Membrane Internalization and is a Dominant Negative Allele , 2010, Scandinavian journal of immunology.

[11]  J. Mege,et al.  Role of the cytoplasmic pattern recognition receptor Nod2 in Coxiella burnetii infection. , 2009, Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases.

[12]  M. Rieder,et al.  Toll-like receptor 1 polymorphisms affect innate immune responses and outcomes in sepsis. , 2008, American journal of respiratory and critical care medicine.

[13]  J. Kalil,et al.  Variants in the toll-like receptor signaling pathway and clinical outcomes of malaria. , 2008, The Journal of infectious diseases.

[14]  Richard D. Wells,et al.  Human TLR1 Deficiency Is Associated with Impaired Mycobacterial Signaling and Protection from Leprosy Reversal Reaction , 2008, PLoS neglected tropical diseases.

[15]  M. Netea,et al.  Mycobacterium paratuberculosis is recognized by Toll‐like receptors and NOD2 , 2007, Journal of leukocyte biology.

[16]  J. Ochoa-Repáraz,et al.  Attenuated Coxiella burnetii Phase II Causes a Febrile Response in Gamma Interferon Knockout and Toll-Like Receptor 2 Knockout Mice and Protects against Reinfection , 2007, Infection and Immunity.

[17]  L. Joosten,et al.  Bartonella quintana Lipopolysaccharide Is a Natural Antagonist of Toll-Like Receptor 4 , 2007, Infection and Immunity.

[18]  S. Akira,et al.  Pathogen Recognition and Innate Immunity , 2006, Cell.

[19]  D. Raoult,et al.  TLR2 Is Necessary to Inflammatory Response in Coxiella burnetii Infection , 2005, Annals of the New York Academy of Sciences.

[20]  J. Satagopan,et al.  TLR1 and TLR6 Polymorphisms Are Associated with Susceptibility to Invasive Aspergillosis after Allogeneic Stem Cell Transplantation , 2005, Annals of the New York Academy of Sciences.

[21]  M. Netea,et al.  NOD2 3020insC mutation and the pathogenesis of Crohn's disease: impaired IL-1beta production points to a loss-of-function phenotype. , 2005, The Netherlands journal of medicine.

[22]  D. Raoult,et al.  Natural history and pathophysiology of Q fever. , 2005, The Lancet. Infectious diseases.

[23]  I. C. Almeida,et al.  Stimulation of Toll-like Receptor 2 by Coxiella burnetii Is Required for Macrophage Production of Pro-inflammatory Cytokines and Resistance to Infection* , 2004, Journal of Biological Chemistry.

[24]  S. Akira,et al.  Lipopolysaccharide from Coxiella burnetii Is Involved in Bacterial Phagocytosis, Filamentous Actin Reorganization, and Inflammatory Responses through Toll-Like Receptor 41 , 2004, The Journal of Immunology.

[25]  C. Hughes,et al.  Of Mice and Not Men: Differences between Mouse and Human Immunology , 2004, The Journal of Immunology.

[26]  R. Toman,et al.  Structural Properties of Lipopolysaccharides from Coxiella burnetii Strains Henzerling and S , 2003, Annals of the New York Academy of Sciences.

[27]  S. Akira,et al.  Cutting Edge: Role of Toll-Like Receptor 1 in Mediating Immune Response to Microbial Lipoproteins1 , 2002, The Journal of Immunology.

[28]  C. Janeway,et al.  RICK/Rip2/CARDIAK mediates signalling for receptors of the innate and adaptive immune systems , 2002, Nature.

[29]  Huitu Liu,et al.  MAPK signal pathways in the regulation of cell proliferation in mammalian cells , 2002, Cell Research.

[30]  Ruslan Medzhitov,et al.  Toll-like receptors and innate immunity , 2001, Nature Reviews Immunology.

[31]  S. Akira,et al.  Discrimination of bacterial lipoproteins by Toll-like receptor 6. , 2001, International immunology.

[32]  D. Raoult,et al.  Interleukin-10 Stimulates Coxiella burnetiiReplication in Human Monocytes through Tumor Necrosis Factor Down-Modulation: Role in Microbicidal Defect of Q Fever , 2001, Infection and Immunity.

[33]  A. Aderem,et al.  The repertoire for pattern recognition of pathogens by the innate immune system is defined by cooperation between toll-like receptors. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[34]  D. Golenbock,et al.  Lipid A-like molecules that antagonize the effects of endotoxins on human monocytes. , 1991, The Journal of biological chemistry.

[35]  P. Hitchcock,et al.  Morphological heterogeneity among Salmonella lipopolysaccharide chemotypes in silver-stained polyacrylamide gels , 1983, Journal of bacteriology.

[36]  C. Galanos,et al.  Lipid A component of lipopolysaccharides from Coxiella burnetii. , 1981, Acta virologica.

[37]  G. Argast,et al.  Inhibition of RIP2/RICK/CARDIAK activity by pyridinyl imidazole inhibitors of p38 MAPK , 2005, Molecular and Cellular Biochemistry.