Skip to main content

Interaction of Leptospira with the Innate Immune System

  • Chapter
  • First Online:

Part of the book series: Current Topics in Microbiology and Immunology ((CT MICROBIOLOGY,volume 415))

Abstract

Innate immunity encompasses immediate host responses that detect and respond to microbes. Besides recognition by the complement system (see the chapter by A. Barbosa, this volume), innate immunity concerns cellular responses. These are triggered through recognition of conserved microbial components (called MAMPs) by pattern recognition receptors (PRRs), leading, through secretion of cytokines, antimicrobial peptides, and immune mediators, to cellular recruitment and phagocytosis. Leptospira spp. are successful zoonotic pathogenic bacteria that obviously overcome the immune system of their hosts. The first part of this chapter summarizes what is known about leptospires recognition and interaction with phagocytes and other innate immune cells, and the second part describes specific interactions of leptospiral MAMPs with PRRs from the TLR and NLR families. On the one hand, pathogenic leptospires appear to escape macrophage and neutrophil phagocytosis. On the other hand, studies about PRR sensing of leptospires remain very limited, but suggest that pathogenic leptospires escape some of the PRRs in a host-specific manner, due to peculiar cell wall specificities or post-translational modifications that may impair their recognition. Further studies are necessary to clarify the mechanisms and consequences of leptospiral escape on phagocytic functions and hopefully give clues to potential therapeutic strategies aimed at restoring the defective activation of PRRs by pathogenic Leptospira spp.

This is a preview of subscription content, log in via an institution.

Abbreviations

BMM:

Bone marrow-derived macrophages

GLP:

Glycolipoprotein

Ig:

Immunoglobulins

LPS:

Lipopolysaccharide

LRR:

Leucine reach repeat

MAMP:

Microbe-associated molecular patterns

Na/K-ATPase:

Potassium pump

NLR:

NOD-like receptor

PBMC:

Peripheral blood mononuclear cell

PRR:

Pattern recognition receptor

TLR:

Toll-like receptor

References

  • Adler B (2014) Pathogenesis of leptospirosis: cellular and molecular aspects. Vet Microbiol 172:353–358

    Article  CAS  PubMed  Google Scholar 

  • Adler B, Faine S (1976) Susceptibility of mice treated with cyclophosphamide to lethal infection with Leptospira interrogans Serovar pomona. Infect Immun 14:703–708

    CAS  PubMed  PubMed Central  Google Scholar 

  • Banfi E, Cinco M, Bellini M, Soranzo MR (1982) The role of antibodies and serum complement in the interaction between macrophages and leptospires. J Gen Microbiol 128:813–816

    CAS  PubMed  Google Scholar 

  • Barry M, Wisnewski AV, Matthias MA, Inouye SK, Vinetz JM (2006) Suburban leptospirosis: atypical lymphocytosis and gamma-delta T cell response. Clin Infect Dis 43:1304–1307

    Article  PubMed  Google Scholar 

  • Bens M, Vimont S, Ben Mkaddem S, Chassin C, Goujon JM, Balloy V, Chignard M, Werts C, Vandewalle A (2014) Flagellin/TLR5 signalling activates renal collecting duct cells and facilitates invasion and cellular translocation of uropathogenic Escherichia coli. Cell Microbiol 16:1503–1517

    Article  CAS  PubMed  Google Scholar 

  • Blasi E, Ardizzoni A, Colombari B, Neglia R, Baschieri C, Peppoloni S, Cinco M (2007) NF-kB activation and p38 phosphorylation in microglial cells infected with Leptospira or exposed to partially purified leptospiral lipoproteins. Microb Pathog 42:80–87

    Article  CAS  PubMed  Google Scholar 

  • Cedola M, Chiani Y, Pretre G, Alberdi L, Vanasco B, Gomez RM (2015) Association of Toll-like receptor 2 Arg753Gln and Toll-like receptor 1 Ile602Ser single-nucleotide polymorphisms with leptospirosis in an Argentine population. Acta Trop 146:73–80

    Article  CAS  PubMed  Google Scholar 

  • Cesar KR, Romero EC, de Braganca AC, Blanco RM, Abreu PA, Magaldi AJ (2012) Renal involvement in leptospirosis: the effect of glycolipoprotein on renal water absorption. PLoS ONE 7:e37625

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  • Chagan-Yasutan H, Chen Y, Lacuesta TL, Leano PS, Iwasaki H, Hanan F, Taurustiati D, Ohmoto Y, Ashino Y, Saitoh H, Kiyomoto H, Suzuki Y, Telan FO, Hattori T (2016). Urine levels of defensin α1 reflect kidney injury in leptospirosis patients. Int J Mol Sci 17(10):1637

    Google Scholar 

  • Challa S, Nally JE, Jones C, Sheoran AS (2011) Passive immunization with Leptospira LPS-specific agglutinating but not non-agglutinating monoclonal antibodies protect guinea pigs from fatal pulmonary hemorrhages induced by serovar Copenhageni challenge. Vaccine 29:4431–4434

    Article  CAS  PubMed  Google Scholar 

  • Chang MY, Cheng YC, Hsu SH, Ma TL, Chou LF, Hsu HH, Tian YC, Chen YC, Sun YJ, Hung CC, Pan RL, Yang CW (2016) Leptospiral outer membrane protein LipL32 induces inflammation and kidney injury in zebrafish larvae. Sci Rep 6:27838

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  • Chassin C, Picardeau M, Goujon JM, Bourhy P, Quellard N, Darche S, Badell E, d’Andon MF, Winter N, Lacroix-Lamande S, Buzoni-Gatel D, Vandewalle A, Werts C (2009) TLR4- and TLR2-mediated B cell responses control the clearance of the bacterial pathogen, Leptospira interrogans. J Immunol 183:2669–2677

    Article  CAS  PubMed  Google Scholar 

  • Cinco M, Banfi E, Soranzo MR (1981) Studies on the interaction between macrophages and leptospires. J Gen Microbiol 124:409–413

    CAS  PubMed  Google Scholar 

  • Cinco M, Vecile E, Murgia R, Dobrina P, Dobrina A (1996) Leptospira interrogans and Leptospira peptidoglycans induce the release of tumor necrosis factor alpha from human monocytes. FEMS Microbiol Lett 138:211–214

    Article  CAS  PubMed  Google Scholar 

  • Craig SB, Collet TA, Wynwood SJ, Smythe LD, Weier SL, McKay DB (2013) Neutrophil counts in leptospirosis patients infected with different serovars. Trop Biomed 30:579–583

    CAS  PubMed  Google Scholar 

  • Damasco PV, Avila CA, Barbosa AT, Ribeiro Carvalho Mde M, Pereira GM, Lemos ER, Boia MN, Pereira MM (2011) Atypical lymphocytosis in leptospirosis: a cohort of hospitalized cases between 1996 and 2009 in State of Rio de Janeiro, Brazil. Rev Soc Bras Med Trop 44:611–615

    Article  PubMed  Google Scholar 

  • Davis JM, Haake DA, Ramakrishnan L (2009) Leptospira interrogans stably infects zebrafish embryos, altering phagocyte behavior and homing to specific tissues. PLoS Negl Trop Dis 3:e463

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • De Silva NL, Niloofa M, Fernando N, Karunanayake L, Rodrigo C, De Silva HJ, Premawansa S, Handunnetti SM, Rajapakse S (2014) Changes in full blood count parameters in leptospirosis: a prospective study. Int Arch Med 7:31

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Diament D, Brunialti MK, Romero EC, Kallas EG, Salomao R (2002) Peripheral blood mononuclear cell activation induced by Leptospira interrogans glycolipoprotein. Infect Immun 70:1677–1683

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dorigatti F, Brunialti MK, Romero EC, Kallas EG, Salomao R (2005) Leptospira interrogans activation of peripheral blood monocyte glycolipoprotein demonstrated in whole blood by the release of IL-6. Braz J Med Biol Res 38:909–914

    Article  CAS  PubMed  Google Scholar 

  • Eshghi A, Henderson J, Trent MS, Picardeau M (2015) Leptospira interrogans lpxD homologue is required for thermal acclimatization and virulence. Infect Immun 83:4314–4321

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Faine S, Shahar A, Aronson M (1964) Phagocytosis and its significance in leptospiral infection. Aust J Exp Biol Med Sci 42:579–588

    Article  CAS  PubMed  Google Scholar 

  • Fanton d’Andon M, Quellard N, Fernandez B, Ratet G, Lacroix-Lamande S, Vandewalle A, Boneca IG, Goujon JM, Werts C (2014) Leptospira interrogans induces fibrosis in the mouse kidney through Inos-dependent, TLR- and NLR-independent signaling pathways. PLoS Negl Trop Dis 8:e2664

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Fritz JH, Le Bourhis L, Sellge G, Magalhaes JG, Fsihi H, Kufer TA, Collins C, Viala J, Ferrero RL, Girardin SE, Philpott DJ (2007) Nod1-mediated innate immune recognition of peptidoglycan contributes to the onset of adaptive immunity. Immunity 26:445–459

    Article  CAS  PubMed  Google Scholar 

  • Gaudart N, Ekpo P, Pattanapanyasat K, van Kooyk Y, Engering A (2008) Leptospira interrogans is recognized through DC-SIGN and induces maturation and cytokine production by human dendritic cells. FEMS Immunol Med Microbiol 53:359–367

    Article  CAS  PubMed  Google Scholar 

  • Goncalves-de-Albuquerque CF, Burth P, Silva AR, de Moraes IM, Oliveira FM, Santelli RE, Freire AS, de Lima GS, da Silva ED, da Silva CI, Morandi V, Bozza PT, de Younes-Ibrahim M, Castro Faria Neto HC, de Castro Faria MV (2014) Murine lung injury caused by Leptospira interrogans glycolipoprotein, a specific Na/K-ATPase inhibitor. Respir Res 15:93

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Gordon S (2016) Phagocytosis: an immunobiologic process. Immunity 44:463–475

    Article  CAS  PubMed  Google Scholar 

  • Goris MG, Wagenaar JF, Hartskeerl RA, van Gorp EC, Schuller S, Monahan AM, Nally JE, van der Poll T, van’t Veer C (2011) Potent innate immune response to pathogenic leptospira in human whole blood. PLoS ONE 6:e18279

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  • Guo Y, Fukuda T, Nakamura S, Bai L, Xu J, Kuroda K, Tomioka R, Yoneyama H, Isogai E (2015) Interaction between leptospiral lipopolysaccharide and Toll-like receptor 2 in pig fibroblast cell line, and inhibitory effect of antibody against leptospiral lipopolysaccharide on interaction. Asian-Australas J Anim Sci 28:273–279

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Guo Y, Ding C, Zhang B, Xu J, Xun M, Xu J (2016) Inhibitory effect of BMAP-28 on Leptospiral lipopolysaccharide-induced TLR2-dependent immune response in bovine cells. Jundishapur J Microbiol 9:e33926

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Haake DA, Chao G, Zuerner RL, Barnett JK, Barnett D, Mazel M, Matsunaga J, Levett PN, Bolin CA (2000) The leptospiral major outer membrane protein LipL32 is a lipoprotein expressed during mammalian infection. Infect Immun 68:2276–2285

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hsu SH, Lo YY, Tung JY, Ko YC, Sun YJ, Hung CC, Yang CW, Tseng FG, Fu CC, Pan RL (2010) Leptospiral outer membrane lipoprotein LipL32 binding on Toll-like receptor 2 of renal cells as determined with an atomic force microscope. Biochemistry 49:5408–5417

    Article  CAS  PubMed  Google Scholar 

  • Hu W, Ge Y, Ojcius DM, Sun D, Dong H, Yang XF, Yan J (2013) p53 signalling controls cell cycle arrest and caspase-independent apoptosis in macrophages infected with pathogenic Leptospira species. Cell Microbiol 15:1642–1659

    PubMed  Google Scholar 

  • Hung CC, Chang CT, Chen KH, Tian YC, Wu MS, Pan MJ, Vandewalle A, Yang CW (2006a) Upregulation of chemokine CXCL1/KC by leptospiral membrane lipoprotein preparation in renal tubule epithelial cells. Kidney Int 69:1814–1822

    Article  CAS  PubMed  Google Scholar 

  • Hung CC, Chang CT, Tian YC, Wu MS, Yu CC, Pan MJ, Vandewalle A, Yang CW (2006b) Leptospiral membrane proteins stimulate pro-inflammatory chemokines secretion by renal tubule epithelial cells through Toll-like receptor 2 and p38 mitogen activated protein kinase. Nephrol Dial Transplant 21:898–910

    Article  CAS  PubMed  Google Scholar 

  • Isogai E, Kitagawa H, Isogai H, Kurebayashi Y, Ito N (1986) Phagocytosis as a defense mechanism against infection with leptospiras. Zentralbl Bakteriol Mikrobiol Hyg A 261:65–74

    CAS  PubMed  Google Scholar 

  • Isogai E, Isogai H, Wakizaka H, Miura H, Kurebayashi Y (1989) Chemiluminescence and phagocytic responses of rat polymorphonuclear neutrophils to leptospires. Zentralbl Bakteriol 272:36–46

    Article  CAS  PubMed  Google Scholar 

  • Isogai E, Isogai H, Fujii N, Oguma K (1990a) Biological effects of leptospiral lipopolysaccharide to mouse B, T and NK cells. Nihon Juigaku Zasshi 52:923–930

    Article  CAS  PubMed  Google Scholar 

  • Isogai E, Isogai H, Fujii N, Oguma K (1990b) Macrophage activation by leptospiral lipopolysaccharide. Zentralbl Bakteriol 273:200–208

    Article  CAS  PubMed  Google Scholar 

  • Jayaraman PA, Devlin AA, Miller JC, Scholle F (2016) The adaptor molecule TRIF contributes to murine host defense during leptospiral infection. Immunobiology 221:964–974

    Article  CAS  PubMed  Google Scholar 

  • Jin D, Ojcius DM, Sun D, Dong H, Luo Y, Mao Y, Yan J (2009) Leptospira interrogans induces apoptosis in macrophages via caspase-8- and caspase-3-dependent pathways. Infect Immun 77:799–809

    Article  CAS  PubMed  Google Scholar 

  • Klimpel GR, Matthias MA, Vinetz JM (2003) Leptospira interrogans activation of human peripheral blood mononuclear cells: preferential expansion of TCR gamma delta+ T cells vs TCR alpha beta+ T cells. J Immunol 171:1447–1455

    Article  CAS  PubMed  Google Scholar 

  • Lacroix-Lamande S, d’Andon MF, Michel E, Ratet G, Philpott DJ, Girardin SE, Boneca IG, Vandewalle A, Werts C (2012) Downregulation of the Na/K-ATPase pump by leptospiral glycolipoprotein activates the NLRP3 inflammasome. J Immunol 188:2805–2814

    Article  CAS  PubMed  Google Scholar 

  • Li L, Ojcius DM, Yan J (2007) Comparison of invasion of fibroblasts and macrophages by high- and low-virulence Leptospira strains: colonization of the host-cell nucleus and induction of necrosis by the virulent strain. Arch Microbiol 188:591–598

    Article  CAS  PubMed  Google Scholar 

  • Li S, Ojcius DM, Liao S, Li L, Xue F, Dong H, Yan J (2010) Replication or death: distinct fates of pathogenic Leptospira strain Lai within macrophages of human or mouse origin. Innate Immun 16:80–92

    Article  PubMed  Google Scholar 

  • Lindow JC, Wunder EA Jr, Popper SJ, Min JN, Mannam P, Srivastava A, Yao Y, Hacker KP, Raddassi K, Lee PJ, Montgomery RR, Shaw AC, Hagan JE, Araujo GC, Nery N Jr, Relman DA, Kim CC, Reis MG, Ko AI (2016) Cathelicidin insufficiency in patients with fatal leptospirosis. PLoS Pathog 12:e1005943

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Liu B, Wang Y, Guo X, Zhu W, Zhang Y, He P (2014) Carboxyfluorescein diacetate succinimidyl ester labeling method to study the interaction between Leptospira and macrophages. J Microbiol Methods 107:205–213

    Article  CAS  PubMed  Google Scholar 

  • Lo YY, Hsu SH, Ko YC, Hung CC, Chang MY, Hsu HH, Pan MJ, Chen YW, Lee CH, Tseng FG, Sun YJ, Yang CW, Pan RL (2013) Essential calcium-binding cluster of Leptospira LipL32 protein for inflammatory responses through the Toll-like receptor 2 pathway. J Biol Chem 288:12335–12344

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Marcsisin RA, Bartpho T, Bulach DM, Srikram A, Sermswan RW, Adler B, Murray GL (2013) Use of a high-throughput screen to identify Leptospira mutants unable to colonize the carrier host or cause disease in the acute model of infection. J Med Microbiol 62:1601–1608

    Article  CAS  PubMed  Google Scholar 

  • Matsui M, Rouleau V, Bruyere-Ostells L, Goarant C (2011) Gene expression profiles of immune mediators and histopathological findings in animal models of leptospirosis: comparison between susceptible hamsters and resistant mice. Infect Immun 79:4480–4492

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • McGrath H, Adler B, Vinh T, Faine S (1984) Phagocytosis of virulent and avirulent leptospires by guinea-pig and human polymorphonuclear leukocytes in vitro. Pathology 16:243–249

    Article  CAS  PubMed  Google Scholar 

  • Merien F, Baranton G, Perolat P (1997) Invasion of Vero cells and induction of apoptosis in macrophages by pathogenic Leptospira interrogans are correlated with virulence. Infect Immun 65:729–738

    CAS  PubMed  PubMed Central  Google Scholar 

  • Midwinter A, Faine S, Adler B (1990) Vaccination of mice with lipopolysaccharide (LPS) and LPS-derived immuno-conjugates from Leptospira interrogans. J Med Microbiol 33:199–204

    Article  CAS  PubMed  Google Scholar 

  • Murray GL, Srikram A, Hoke DE, Wunder EA Jr, Henry R, Lo M, Zhang K, Sermswan RW, Ko AI, Adler B (2009) Major surface protein LipL32 is not required for either acute or chronic infection with Leptospira interrogans. Infect Immun 77:952–958

    Article  CAS  PubMed  Google Scholar 

  • Murray GL, Srikram A, Henry R, Hartskeerl RA, Sermswan RW, Adler B (2010) Mutations affecting Leptospira interrogans lipopolysaccharide attenuate virulence. Mol Microbiol 78:701–709

    Article  CAS  PubMed  Google Scholar 

  • Nahori MA, Fournie-Amazouz E, Que-Gewirth NS, Balloy V, Chignard M, Raetz CR, Saint Girons I, Werts C (2005) Differential TLR recognition of leptospiral lipid A and lipopolysaccharide in murine and human cells. J Immunol 175:6022–6031

    Article  CAS  PubMed  Google Scholar 

  • Nally JE, Chow E, Fishbein MC, Blanco DR, Lovett MA (2005) Changes in lipopolysaccharide O antigen distinguish acute versus chronic Leptospira interrogans infections. Infect Immun 73:3251–3260

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Papa A, Kotrotsiou T (2015) Cytokines in human leptospirosis. Trans R Soc Trop Med Hyg 109:749–754

    Article  CAS  PubMed  Google Scholar 

  • Park BS, Song DH, Kim HM, Choi BS, Lee H, Lee JO (2009) The structural basis of lipopolysaccharide recognition by the TLR4-MD-2 complex. Nature 458:1191–1195

    Article  ADS  CAS  PubMed  Google Scholar 

  • Pereira MM, Andrade J, Marchevsky RS, Ribeiro dos Santos R (1998) Morphological characterization of lung and kidney lesions in C3H/HeJ mice infected with Leptospira interrogans serovar icterohaemorrhagiae: defect of CD4+ and CD8+ T-cells are prognosticators of the disease progression. Exp Toxicol Pathol 50:191–198

    Article  CAS  PubMed  Google Scholar 

  • Pinne M, Haake DA (2013) LipL32 is a subsurface lipoprotein of Leptospira interrogans: presentation of new data and reevaluation of previous studies. PLoS ONE 8:e51025

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  • Que-Gewirth NL, Ribeiro AA, Kalb SR, Cotter RJ, Bulach DM, Adler B, Girons IS, Werts C, Raetz CR (2004) A methylated phosphate group and four amide-linked acyl chains in Leptospira interrogans lipid A. The membrane anchor of an unusual lipopolysaccharide that activates TLR2. J Biol Chem 279:25420–25429

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Raffray L, Giry C, Thirapathi Y, Binois F, Moiton MP, Lagrange-Xelot M, Ferrandiz D, Jaffar-Bandjee MC, Gasque P (2015) High leptospiremia is associated with low gamma-delta T cell counts. Microbes Infect 17:451–455

    Article  CAS  PubMed  Google Scholar 

  • Raffray L, Giry C, Vandroux D, Kuli B, Randrianjohany A, Pequin AM, Renou F, Jaffar-Bandjee MC, Gasque P (2016) Major neutrophilia observed in acute phase of human leptospirosis is not associated with increased expression of granulocyte cell activation markers. PLoS ONE 11:e0165716

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Ratet G, Veyrier FJ, Fanton d’Andon M, Kammerscheit X, Nicola MA, Picardeau M, Boneca IG, Werts C (2014) Live imaging of bioluminescent Leptospira interrogans in mice reveals renal colonization as a stealth escape from the blood defenses and antibiotics. PLoS Negl Trop Dis 8:e3359

    Article  PubMed  PubMed Central  Google Scholar 

  • Reynolds JM, Dong C (2013) Toll-like receptor regulation of effector T lymphocyte function. Trends Immunol 34:511–519

    Article  CAS  PubMed  Google Scholar 

  • Richer L, Potula HH, Melo R, Vieira A, Gomes-Solecki M (2015) Mouse model for sublethal Leptospira interrogans infection. Infect Immun 83:4693–4700

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rittig MG, Jagoda JC, Wilske B, Murgia R, Cinco M, Repp R, Burmester GR, Krause A (1998) Coiling phagocytosis discriminates between different spirochetes and is enhanced by phorbol myristate acetate and granulocyte-macrophage colony-stimulating factor. Infect Immun 66:627–635

    CAS  PubMed  PubMed Central  Google Scholar 

  • Saitoh S, Akashi S, Yamada T, Tanimura N, Kobayashi M, Konno K, Matsumoto F, Fukase K, Kusumoto S, Nagai Y, Kusumoto Y, Kosugi A, Miyake K (2004) Lipid A antagonist, lipid IVa, is distinct from lipid A in interaction with Toll-like receptor 4 (TLR4)-MD-2 and ligand-induced TLR4 oligomerization. Int Immunol 16:961–969

    Article  CAS  PubMed  Google Scholar 

  • Sambri V, Marangoni A, Giacani L, Gennaro R, Murgia R, Cevenini R, Cinco M (2002) Comparative in vitro activity of five cathelicidin-derived synthetic peptides against Leptospira, Borrelia and Treponema pallidum. J Antimicrob Chemother 50:895–902

    Article  CAS  PubMed  Google Scholar 

  • Scharrig E, Carestia A, Ferrer MF, Cedola M, Pretre G, Drut R, Picardeau M, Schattner M, Gomez RM (2015) Neutrophil extracellular traps are involved in the innate immune response to infection with Leptospira. PLoS Negl Trop Dis 9:e0003927

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Segal AW (2005) How neutrophils kill microbes. Annu Rev Immunol 23:197–223

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Selsted ME, Ouellette AJ (2005) Mammalian defensins in the antimicrobial immune response. Nat Immunol 6:551–557

    Article  CAS  PubMed  Google Scholar 

  • Slamti L, de Pedro MA, Guichet E, Picardeau M (2011) Deciphering morphological determinants of the helix-shaped Leptospira. J Bacteriol 193:6266–6275

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Souza-Fonseca-Guimaraes F, Adib-Conquy M, Cavaillon JM (2012) Natural killer (NK) cells in antibacterial innate immunity: angels or devils? Mol Med 18:270–285

    Article  CAS  PubMed  Google Scholar 

  • Toma C, Okura N, Takayama C, Suzuki T (2011) Characteristic features of intracellular pathogenic Leptospira in infected murine macrophages. Cell Microbiol 13:1783–1792

    Article  CAS  PubMed  Google Scholar 

  • Toma C, Murray GL, Nohara T, Mizuyama M, Koizumi N, Adler B, Suzuki T (2014) Leptospiral outer membrane protein LMB216 is involved in enhancement of phagocytic uptake by macrophages. Cell Microbiol 16:1366–1377

    Article  CAS  PubMed  Google Scholar 

  • Tourneur E, Ben Mkaddem S, Chassin C, Bens M, Goujon JM, Charles N, Pellefigues C, Aloulou M, Hertig A, Monteiro RC, Girardin SE, Philpott DJ, Rondeau E, Elbim C, Werts C, Vandewalle A (2013) Cyclosporine A impairs nucleotide binding oligomerization domain (Nod1)-mediated innate antibacterial renal defenses in mice and human transplant recipients. PLoS Pathog 9:e1003152

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Truong KN, Coburn J (2011) The emergence of severe pulmonary hemorrhagic leptospirosis: questions to consider. Front Cell Infect Microbiol 1:24

    PubMed  Google Scholar 

  • Veiga E, Cossart P (2006) The role of clathrin-dependent endocytosis in bacterial internalization. Trends Cell Biol 16:499–504

    Article  CAS  PubMed  Google Scholar 

  • Viala J, Chaput C, Boneca IG, Cardona A, Girardin SE, Moran AP, Athman R, Memet S, Huerre MR, Coyle AJ, DiStefano PS, Sansonetti PJ, Labigne A, Bertin J, Philpott DJ, Ferrero RL (2004) Nod1 responds to peptidoglycan delivered by the Helicobacter pylori cag pathogenicity island. Nat Immunol 5:1166–1174

    Article  CAS  PubMed  Google Scholar 

  • Vinh T, Adler B, Faine S (1986) Glycolipoprotein cytotoxin from Leptospira interrogans serovar copenhageni. J Gen Microbiol 132:111–123

    CAS  PubMed  Google Scholar 

  • Viriyakosol S, Matthias MA, Swancutt MA, Kirkland TN, Vinetz JM (2006) Toll-like receptor 4 protects against lethal Leptospira interrogans serovar icterohaemorrhagiae infection and contributes to in vivo control of leptospiral burden. Infect Immun 74:887–895

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wagenaar JF, Gasem MH, Goris MG, Leeflang M, Hartskeerl RA, van der Poll T, van’t Veer C, van Gorp EC (2009) Soluble ST2 levels are associated with bleeding in patients with severe leptospirosis. PLoS Negl Trop Dis 3:e453

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Wang B, Sullivan J, Sullivan GW, Mandell GL (1984a) Interaction of leptospires with human polymorphonuclear neutrophils. Infect Immun 44:459–464

    CAS  PubMed  PubMed Central  Google Scholar 

  • Wang B, Sullivan JA, Sullivan GW, Mandell GL (1984b) Role of specific antibody in interaction of leptospires with human monocytes and monocyte-derived macrophages. Infect Immun 46:809–813

    CAS  PubMed  PubMed Central  Google Scholar 

  • Werts C (2010) Leptospirosis: a Toll road from B lymphocytes. Chang Gung Med J 33:591–601

    PubMed  Google Scholar 

  • Werts C, Tapping RI, Mathison JC, Chuang TH, Kravchenko V, Saint Girons I, Haake DA, Godowski PJ, Hayashi F, Ozinsky A, Underhill DM, Kirschning CJ, Wagner H, Aderem A, Tobias PS, Ulevitch RJ (2001) Leptospiral lipopolysaccharide activates cells through a TLR2-dependent mechanism. Nat Immunol 2:346–352

    Article  CAS  PubMed  Google Scholar 

  • Werts C, Girardin SE, Philpott DJ (2006) TIR, CARD and PYRIN: three domains for an antimicrobial triad. Cell Death Differ 13:798–815

    Article  CAS  PubMed  Google Scholar 

  • Wilson-Welder JH, Frank AT, Hornsby RL, Olsen SC, Alt DP (2016) Interaction of bovine peripheral blood polymorphonuclear cells and Leptospira species; Innate responses in the natural bovine reservoir host. Front Microbiol 7:1110

    Article  PubMed  PubMed Central  Google Scholar 

  • Witchell TD, Eshghi A, Nally JE, Hof R, Boulanger MJ, Wunder EA Jr, Ko AI, Haake DA, Cameron CE (2014) Post-translational modification of LipL32 during Leptospira interrogans infection. PLoS Negl Trop Dis 8:e3280

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Xie JX, Li X, Xie Z (2013) Regulation of renal function and structure by the signaling Na/K-ATPase. IUBMB Life 65:991–998

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Xue F, Zhao X, Yang Y, Zhao J, Yang Y, Cao Y, Hong C, Liu Y, Sun L, Huang M, Gu J (2013) Responses of murine and human macrophages to leptospiral infection: a study using comparative array analysis. PLoS Negl Trop Dis 7:e2477

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Yanagihara Y, Kamisango K, Yasuda S, Kobayashi S, Mifuchi I, Azuma I, Yamamura Y, Johnson RC (1984) Chemical compositions of cell walls and polysaccharide fractions of spirochetes. Microbiol Immunol 28:535–544

    Article  CAS  PubMed  Google Scholar 

  • Yang CW (2007) Leptospirosis renal disease: understanding the initiation by Toll-like receptors. Kidney Int 72:918–925

    Article  CAS  PubMed  Google Scholar 

  • Yang CW, Hung CC, Wu MS, Tian YC, Chang CT, Pan MJ, Vandewalle A (2006) Toll-like receptor 2 mediates early inflammation by leptospiral outer membrane proteins in proximal tubule cells. Kidney Int 69:815–822

    Article  CAS  PubMed  Google Scholar 

  • Zhang L, Zhang C, Ojcius DM, Sun D, Zhao J, Lin X, Li L, Li L, Yan J (2012) The mammalian cell entry (Mce) protein of pathogenic Leptospira species is responsible for RGD motif-dependent infection of cells and animals. Mol Microbiol 83:1006–1023

    Article  CAS  PubMed  Google Scholar 

  • Zhang W, Zhang N, Xie X, Guo J, Jin X, Xue F, Ding Z, Cao Y (2016). TLR2 agonist Pam3CSK4 alleviates the pathology of leptospirosis in hamster. Infect Immun 84(12):3350–3357

    Google Scholar 

  • Zuerner RL, Alt DP, Palmer MV, Thacker TC, Olsen SC. ( 2011) A Leptospira borgpetersenii serovar Hardjo vaccine induces a Th1 response, activates NK cells, and reduces renal colonization. Clin Vaccine Immunol 18(4):684–691. doi:10.1128/CVI.00288-10. Epub 2011 Feb 2. PMID:21288995

Download references

Acknowledgements

We thank Richard Wheeler for English editing and Ignacio Santecchia for the illustration, using resources from Servier Medical Art (www.servier.com).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Catherine Werts .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2017 Springer International Publishing AG

About this chapter

Cite this chapter

Werts, C. (2017). Interaction of Leptospira with the Innate Immune System. In: Adler, B. (eds) Spirochete Biology: The Post Genomic Era. Current Topics in Microbiology and Immunology, vol 415. Springer, Cham. https://doi.org/10.1007/82_2017_46

Download citation

Publish with us

Policies and ethics