Cellular and Molecular Life Sciences

, Volume 73, Issue 6, pp 1225–1236 | Cite as

Exploring NAD+ metabolism in host–pathogen interactions

  • Inês Mesquita
  • Patrícia Varela
  • Ana Belinha
  • Joana Gaifem
  • Mireille Laforge
  • Baptiste Vergnes
  • Jérôme Estaquier
  • Ricardo Silvestre


Nicotinamide adenine dinucleotide (NAD+) is a vital molecule found in all living cells. NAD+ intracellular levels are dictated by its synthesis, using the de novo and/or salvage pathway, and through its catabolic use as co-enzyme or co-substrate. The regulation of NAD+ metabolism has proven to be an adequate drug target for several diseases, including cancer, neurodegenerative or inflammatory diseases. Increasing interest has been given to NAD+ metabolism during innate and adaptive immune responses suggesting that its modulation could also be relevant during host–pathogen interactions. While the maintenance of NAD+ homeostatic levels assures an adequate environment for host cell survival and proliferation, fluctuations in NAD+ or biosynthetic precursors bioavailability have been described during host–pathogen interactions, which will interfere with pathogen persistence or clearance. Here, we review the double-edged sword of NAD+ metabolism during host–pathogen interactions emphasizing its potential for treatment of infectious diseases.


Nicotinamide adenine dinucleotide (NAD+Host-pathogen interaction NAD+/NADH ratio NADPH Sirtuins l-tryptophan 



JG was supported by PD/BD/106053/2015. BV was supported by IRD (Institut de Recherche pour le Développement) institutional funding. JE was supported by a European Community’s Seventh Framework Program under grant agreement No. 602773 (Project KINDRED), an ANR grant (LEISH-APO, France) and a Partenariat Hubert Curien (PHC) (program Volubilis, MA/11/262). JE also thanks the Canada Research Chair program for his support. RS thank FCT—Foundation for Science and Technology—for their Investigator FCT Grant (IF/00021/2014)

Compliance with ethical standards

Conflict of interest

The authors have declared that no competing interests exist.


  1. 1.
    Alano CC, Garnier P, Ying W, Higashi Y, Kauppinen TM, Swanson RA (2010) NAD+ depletion is necessary and sufficient for poly(ADP-ribose) polymerase-1-mediated neuronal death. J Neurosci 30:2967–2978PubMedCentralPubMedCrossRefGoogle Scholar
  2. 2.
    Ariumi Y, Turelli P, Masutani M, Trono D (2005) DNA damage sensors ATM, ATR, DNA-PKcs, and PARP-1 are dispensable for human immunodeficiency virus type 1 integration. J Virol 79:2973–2978PubMedCentralPubMedCrossRefGoogle Scholar
  3. 3.
    Bastiat-Sempe B, Love JF, Lomayesva N, Wessels MR (2014) Streptolysin O and NAD-glycohydrolase prevent phagolysosome acidification and promote group a streptococcus survival in macrophages. mBio 5:e01690-01614CrossRefGoogle Scholar
  4. 4.
    Boasso A (2011) Wounding the immune system with its own blade: HIV-induced tryptophan catabolism and pathogenesis. Curr Med Chem 18:2247–2256PubMedCrossRefGoogle Scholar
  5. 5.
    Brown SA, Palmer KL, Whiteley M (2008) Revisiting the host as a growth medium. Nat Rev Microbiol 6:657–666PubMedCentralPubMedCrossRefGoogle Scholar
  6. 6.
    Bruzzone S, Parenti MD, Grozio A, Ballestrero A, Bauer I, Del Rio A, Nencioni A (2013) Rejuvenating sirtuins: the rise of a new family of cancer drug targets. Curr Pharm Des 19:614–623PubMedCentralPubMedCrossRefGoogle Scholar
  7. 7.
    Bueno MT, Reyes D, Valdes L, Saheba A, Urias E, Mendoza C et al (2013) Poly(ADP-ribose) polymerase 1 promotes transcriptional repression of integrated retroviruses. J Virol 87:2496–2507PubMedCentralPubMedCrossRefGoogle Scholar
  8. 8.
    Burkle A (2005) Poly(ADP-ribose). The most elaborate metabolite of NAD+. FEBS J 272:4576–4589PubMedCrossRefGoogle Scholar
  9. 9.
    Cagnetta A, Soncini D, Caffa I, Acharya C, Acharya P, Adamia S et al (2015) Apo866 increases anti-tumor activity of cyclosporin-a by inducing mitochondrial and endoplasmic reticulum stress in leukemia cells. Clin Cancer Res 21(17):3934–3945PubMedCrossRefGoogle Scholar
  10. 10.
    Cappellini MD, Fiorelli G (2008) Glucose-6-phosphate dehydrogenase deficiency. Lancet 371:64–74PubMedCrossRefGoogle Scholar
  11. 11.
    Cardoso F, Castro F, Moreira-Teixeira L, Sousa J, Torrado E, Silvestre R et al (2015) Myeloid sirtuin 2 expression does not impact long-term Mycobacterium tuberculosis control. PLoS One 10:e0131904PubMedCentralPubMedCrossRefGoogle Scholar
  12. 12.
    Cervantes-Sandoval I, Serrano-Luna Jde J, Garcia-Latorre E, Tsutsumi V, Shibayama M (2008) Characterization of brain inflammation during primary amoebic meningoencephalitis. Parasitol Int 57:307–313PubMedCrossRefGoogle Scholar
  13. 13.
    Chandrasekaran S, Caparon MG (2015) The Streptococcus pyogenes NAD glycohydrolase modulates epithelial cell PARylation and HMGB1 release. Cell Microbiol 17(9):1376–1390PubMedCrossRefGoogle Scholar
  14. 14.
    Chen XY, Zhang HS, Wu TC, Sang WW, Ruan Z (2013) Down-regulation of NAMPT expression by miR-182 is involved in Tat-induced HIV-1 long terminal repeat (LTR) transactivation. Int J Biochem Cell Biol 45:292–298PubMedCrossRefGoogle Scholar
  15. 15.
    Choi J, Corder NL, Koduru B, Wang Y (2014) Oxidative stress and hepatic Nox proteins in chronic hepatitis C and hepatocellular carcinoma. Free Radic Biol Med 72:267–284PubMedCrossRefGoogle Scholar
  16. 16.
    Cumont MC, Monceaux V, Viollet L, Lay S, Parker R, Hurtrel B, Estaquier J (2007) TGF-beta in intestinal lymphoid organs contributes to the death of armed effector CD8 T cells and is associated with the absence of virus containment in rhesus macaques infected with the simian immunodeficiency virus. Cell Death Differ 14:1747–1758PubMedCrossRefGoogle Scholar
  17. 17.
    de Toledo FG, Cheng J, Liang M, Chini EN, Dousa TP (2000) ADP-Ribosyl cyclase in rat vascular smooth muscle cells: properties and regulation. Circ Res 86:1153–1159PubMedCrossRefGoogle Scholar
  18. 18.
    Di Stefano M, Conforti L (2013) Diversification of NAD biological role: the importance of location. FEBS J 280:4711–4728PubMedCrossRefGoogle Scholar
  19. 19.
    Dolle C, Niere M, Lohndal E, Ziegler M (2010) Visualization of subcellular NAD pools and intra-organellar protein localization by poly-ADP-ribose formation. Cell Mol Life Sci 67:433–443PubMedCrossRefGoogle Scholar
  20. 20.
    Domergue R, Castano I, De Las Penas A, Zupancic M, Lockatell V, Hebel JR et al (2005) Nicotinic acid limitation regulates silencing of Candida adhesins during UTI. Science 308:866–870PubMedCrossRefGoogle Scholar
  21. 21.
    Dousa TP, Chini EN, Beers KW (1996) Adenine nucleotide diphosphates: emerging second messengers acting via intracellular Ca2+ release. Am J Physiol 271:C1007–C1024PubMedGoogle Scholar
  22. 22.
    El-Zaatari M, Chang YM, Zhang M, Franz M, Shreiner A, McDermott AJ et al (2014) Tryptophan catabolism restricts IFN-gamma-expressing neutrophils and Clostridium difficile immunopathology. J Immunol 193:807–816PubMedCentralPubMedCrossRefGoogle Scholar
  23. 23.
    Eskandarian HA, Impens F, Nahori MA, Soubigou G, Coppee JY, Cossart P, Hamon MA (2013) A role for SIRT2-dependent histone H3K18 deacetylation in bacterial infection. Science 341:1238858PubMedCrossRefGoogle Scholar
  24. 24.
    Estrada-Figueroa LA, Ramirez-Jimenez Y, Osorio-Trujillo C, Shibayama M, Navarro-Garcia F, Garcia-Tovar C, Talamas-Rohana P (2011) Absence of CD38 delays arrival of neutrophils to the liver and innate immune response development during hepatic amoebiasis by Entamoeba histolytica. Parasite Immunol 33:661–668PubMedCrossRefGoogle Scholar
  25. 25.
    Fouquerel E, Sobol RW (2014) ARTD1 (PARP1) activation and NAD(+) in DNA repair and cell death. DNA Repair (Amst) 23:27–32CrossRefGoogle Scholar
  26. 26.
    Gazanion E, Garcia D, Silvestre R, Gerard C, Guichou JF, Labesse G et al (2011) The Leishmania nicotinamidase is essential for NAD+ production and parasite proliferation. Mol Microbiol 82:21–38PubMedCrossRefGoogle Scholar
  27. 27.
    Grandvaux N, Mariani M, Fink K (2015) Lung epithelial NOX/DUOX and respiratory virus infections. Clin Sci (Lond) 128:337–347CrossRefGoogle Scholar
  28. 28.
    Ha EM, Lee KA, Seo YY, Kim SH, Lim JH, Oh BH et al (2009) Coordination of multiple dual oxidase-regulatory pathways in responses to commensal and infectious microbes in Drosophila gut. Nat Immunol 10:949–957PubMedCrossRefGoogle Scholar
  29. 29.
    Ha EM, Oh CT, Bae YS, Lee WJ (2005) A direct role for dual oxidase in Drosophila gut immunity. Science 310:847–850PubMedCrossRefGoogle Scholar
  30. 30.
    Ha HC, Juluri K, Zhou Y, Leung S, Hermankova M, Snyder SH (2001) Poly(ADP-ribose) polymerase-1 is required for efficient HIV-1 integration. Proc Natl Acad Sci USA 98:3364–3368PubMedCentralPubMedCrossRefGoogle Scholar
  31. 31.
    Hassa PO, Haenni SS, Elser M, Hottiger MO (2006) Nuclear ADP-ribosylation reactions in mammalian cells: Where are we today and where are we going? Microbiol Mol Biol Rev 70:789–829PubMedCentralPubMedCrossRefGoogle Scholar
  32. 32.
    He M, Gao SJ (2014) A novel role of SIRT1 in gammaherpesvirus latency and replication. Cell Cycle 13:3328–3330PubMedCentralPubMedCrossRefGoogle Scholar
  33. 33.
    Hill T 3rd, Xu C, Harper RW (2010) IFNgamma mediates DUOX2 expression via a STAT-independent signaling pathway. Biochem Biophys Res Commun 395:270–274PubMedCentralPubMedCrossRefGoogle Scholar
  34. 34.
    Hogan D, Wheeler RT (2014) The complex roles of NADPH oxidases in fungal infection. Cell Microbiol 16:1156–1167PubMedCentralPubMedCrossRefGoogle Scholar
  35. 35.
    Hoshi M, Saito K, Hara A, Taguchi A, Ohtaki H, Tanaka R et al (2010) The absence of IDO upregulates type I IFN production, resulting in suppression of viral replication in the retrovirus-infected mouse. J Immunol 185:3305–3312PubMedCrossRefGoogle Scholar
  36. 36.
    Houtkooper RH, Pirinen E, Auwerx J (2012) Sirtuins as regulators of metabolism and healthspan. Nat Rev Mol Cell Biol 13:225–238PubMedCrossRefGoogle Scholar
  37. 37.
    Joo JH, Ryu JH, Kim CH, Kim HJ, Suh MS, Kim JO et al (2012) Dual oxidase 2 is essential for the toll-like receptor 5-mediated inflammatory response in airway mucosa. Antioxid Redox Signal 16:57–70PubMedCrossRefGoogle Scholar
  38. 38.
    Kemmer G, Reilly TJ, Schmidt-Brauns J, Zlotnik GW, Green BA, Fiske MJ et al (2001) NadN and e (P4) are essential for utilization of NAD and nicotinamide mononucleotide but not nicotinamide riboside in Haemophilus influenzae. J Bacteriol 183:3974–3981PubMedCentralPubMedCrossRefGoogle Scholar
  39. 39.
    Kim HJ, Kim CH, Kim MJ, Ryu JH, Seong SY, Kim S et al (2015) The Induction of pattern-recognition receptor expression against influenza A virus through Duox2-derived reactive oxygen species in Nasal Mucosa. Am J Respir Cell Mol Biol 53:525–535PubMedCrossRefGoogle Scholar
  40. 40.
    Kim S, Kurokawa D, Watanabe K, Makino S, Shirahata T, Watarai M (2004) Brucella abortus nicotinamidase (PncA) contributes to its intracellular replication and infectivity in mice. FEMS Microbiol Lett 234:289–295PubMedCrossRefGoogle Scholar
  41. 41.
    Kim SH, Lee WJ (2014) Role of DUOX in gut inflammation: lessons from Drosophila model of gut–microbiota interactions. Front Cell Infect Microbiol 3:116PubMedCentralPubMedCrossRefGoogle Scholar
  42. 42.
    Kim UH, Kim MK, Kim JS, Han MK, Park BH, Kim HR (1993) Purification and characterization of NAD glycohydrolase from rabbit erythrocytes. Arch Biochem Biophys 305:147–152PubMedCrossRefGoogle Scholar
  43. 43.
    Koedel U, Winkler F, Angele B, Fontana A, Pfister HW (2002) Meningitis-associated central nervous system complications are mediated by the activation of poly(ADP-ribose) polymerase. J Cereb Blood Flow Metab 22:39–49PubMedCrossRefGoogle Scholar
  44. 44.
    Kurnasov OV, Polanuyer BM, Ananta S, Sloutsky R, Tam A, Gerdes SY, Osterman AL (2002) Ribosylnicotinamide kinase domain of NadR protein: identification and implications in NAD biosynthesis. J Bacteriol 184:6906–6917PubMedCentralPubMedCrossRefGoogle Scholar
  45. 45.
    Lau C, Dolle C, Gossmann TI, Agledal L, Niere M, Ziegler M (2010) Isoform-specific targeting and interaction domains in human nicotinamide mononucleotide adenylyltransferases. J Biol Chem 285:18868–18876PubMedCentralPubMedCrossRefGoogle Scholar
  46. 46.
    Lau C, Niere M, Ziegler M (2009) The NMN/NaMN adenylyltransferase (NMNAT) protein family. Front Biosci (Landmark Ed) 14:410–431CrossRefGoogle Scholar
  47. 47.
    Lee HC (2006) Structure and enzymatic functions of human CD38. Mol Med 12:317–323PubMedCentralPubMedCrossRefGoogle Scholar
  48. 48.
    Li Q, He M, Zhou F, Ye F, Gao SJ (2014) Activation of Kaposi’s sarcoma-associated herpesvirus (KSHV) by inhibitors of class III histone deacetylases: identification of sirtuin 1 as a regulator of the KSHV life cycle. J Virol 88:6355–6367PubMedCentralPubMedCrossRefGoogle Scholar
  49. 49.
    Lu H, Wu Q, Yang H (2015) DUOX2 promotes the elimination of the Klebsiella pneumoniae strain K5 from T24 cells through the reactive oxygen species pathway. Int J Mol Med 36:551–558PubMedGoogle Scholar
  50. 50.
    Magni G, Orsomando G, Raffelli N, Ruggieri S (2008) Enzymology of mammalian NAD metabolism in health and disease. Front Biosci 13:6135–6154PubMedCrossRefGoogle Scholar
  51. 51.
    Mantis NJ, Sansonetti PJ (1996) The nadB gene of Salmonella typhimurium complements the nicotinic acid auxotrophy of Shigella flexneri. Mol Gen Genet 252:626–629PubMedGoogle Scholar
  52. 52.
    Medana IM, Mai NT, Day NP, Hien TT, Bethell D, Phu NH et al (2001) Cellular stress and injury responses in the brains of adult Vietnamese patients with fatal Plasmodium falciparum malaria. Neuropathol Appl Neurobiol 27:421–433PubMedCrossRefGoogle Scholar
  53. 53.
    Michan S, Sinclair D (2007) Sirtuins in mammals: insights into their biological function. Biochem J 404:1–13PubMedCentralPubMedCrossRefGoogle Scholar
  54. 54.
    Michos A, Gryllos I, Hakansson A, Srivastava A, Kokkotou E, Wessels MR (2006) Enhancement of streptolysin O activity and intrinsic cytotoxic effects of the group A streptococcal toxin, NAD-glycohydrolase. J Biol Chem 281:8216–8223PubMedCrossRefGoogle Scholar
  55. 55.
    Mocarski ES, Guo H, Kaiser WJ (2015) Necroptosis: the Trojan horse in cell autonomous antiviral host defense. Virology 479–480:160–166PubMedCrossRefGoogle Scholar
  56. 56.
    Moreira D, Rodrigues V, Abengozar M, Rivas L, Rial E, Laforge M et al (2015) Leishmania infantum modulates host macrophage mitochondrial metabolism by hijacking the SIRT1-AMPK axis. PLoS Pathog 11:e1004684PubMedCentralPubMedCrossRefGoogle Scholar
  57. 57.
    Moreno-Vinasco L, Quijada H, Sammani S, Siegler J, Letsiou E, Deaton R et al (2014) Nicotinamide phosphoribosyltransferase inhibitor is a novel therapeutic candidate in murine models of inflammatory lung injury. Am J Respir Cell Mol Biol 51:223–228PubMedCentralPubMedGoogle Scholar
  58. 58.
    Mori V, Amici A, Mazzola F, Di Stefano M, Conforti L, Magni G et al (2014) Metabolic profiling of alternative NAD biosynthetic routes in mouse tissues. PLoS One 9:e113939PubMedCentralPubMedCrossRefGoogle Scholar
  59. 59.
    Muller S (2004) Redox and antioxidant systems of the malaria parasite Plasmodium falciparum. Mol Microbiol 53:1291–1305PubMedCrossRefGoogle Scholar
  60. 60.
    Murakami Y, Hoshi M, Hara A, Takemura M, Arioka Y, Yamamoto Y et al (2012) Inhibition of increased indoleamine 2,3-dioxygenase activity attenuates Toxoplasma gondii replication in the lung during acute infection. Cytokine 59:245–251PubMedCrossRefGoogle Scholar
  61. 61.
    Murray MF (2003) Nicotinamide: an oral antimicrobial agent with activity against both Mycobacterium tuberculosis and human immunodeficiency virus. Clin Infect Dis 36:453–460PubMedCrossRefGoogle Scholar
  62. 62.
    Murray MF, Nghiem M, Srinivasan A (1995) HIV infection decreases intracellular nicotinamide adenine dinucleotide [NAD]. Biochem Biophys Res Commun 212:126–131PubMedCrossRefGoogle Scholar
  63. 63.
    O’Hara JK, Kerwin LJ, Cobbold SA, Tai J, Bedell TA, Reider PJ, Llinas M (2014) Targeting NAD+ metabolism in the human malaria parasite Plasmodium falciparum. PLoS One 9:e94061PubMedCentralPubMedCrossRefGoogle Scholar
  64. 64.
    O’Seaghdha M, Wessels MR (2013) Streptolysin O and its co-toxin NAD-glycohydrolase protect group A Streptococcus from Xenophagic killing. PLoS Pathog 9:e1003394PubMedCentralPubMedCrossRefGoogle Scholar
  65. 65.
    Olesen UH, Thougaard AV, Jensen PB, Sehested M (2010) A preclinical study on the rescue of normal tissue by nicotinic acid in high-dose treatment with APO866, a specific nicotinamide phosphoribosyltransferase inhibitor. Mol Cancer Ther 9:1609–1617PubMedCrossRefGoogle Scholar
  66. 66.
    Paiva CN, Bozza MT (2014) Are reactive oxygen species always detrimental to pathogens? Antioxid Redox Signal 20:1000–1037PubMedCentralPubMedCrossRefGoogle Scholar
  67. 67.
    Panday A, Sahoo MK, Osorio D, Batra S (2015) NADPH oxidases: an overview from structure to innate immunity-associated pathologies. Cell Mol Immunol 12:5–23PubMedCentralPubMedCrossRefGoogle Scholar
  68. 68.
    Partida-Sanchez S, Cockayne DA, Monard S, Jacobson EL, Oppenheimer N, Garvy B et al (2001) Cyclic ADP-ribose production by CD38 regulates intracellular calcium release, extracellular calcium influx and chemotaxis in neutrophils and is required for bacterial clearance in vivo. Nat Med 7:1209–1216PubMedCrossRefGoogle Scholar
  69. 69.
    Partida-Sanchez S, Rivero-Nava L, Shi G, Lund FE (2007) CD38: an ecto-enzyme at the crossroads of innate and adaptive immune responses. Adv Exp Med Biol 590:171–183PubMedCrossRefGoogle Scholar
  70. 70.
    Pittelli M, Formentini L, Faraco G, Lapucci A, Rapizzi E, Cialdai F et al (2010) Inhibition of nicotinamide phosphoribosyltransferase: cellular bioenergetics reveals a mitochondrial insensitive NAD pool. J Biol Chem 285:34106–34114PubMedCentralPubMedCrossRefGoogle Scholar
  71. 71.
    Prendergast GC, Smith C, Thomas S, Mandik-Nayak L, Laury-Kleintop L, Metz R, Muller AJ (2014) Indoleamine 2,3-dioxygenase pathways of pathogenic inflammation and immune escape in cancer. Cancer Immunol Immunother 63:721–735PubMedCentralPubMedCrossRefGoogle Scholar
  72. 72.
    Prunier AL, Schuch R, Fernandez RE, Maurelli AT (2007) Genetic structure of the nadA and nadB antivirulence loci in Shigella spp. J Bacteriol 189:6482–6486PubMedCentralPubMedCrossRefGoogle Scholar
  73. 73.
    Prunier AL, Schuch R, Fernandez RE, Mumy KL, Kohler H, McCormick BA, Maurelli AT (2007) nadA and nadB of Shigella flexneri 5a are antivirulence loci responsible for the synthesis of quinolinate, a small molecule inhibitor of Shigella pathogenicity. Microbiology 153:2363–2372PubMedCrossRefGoogle Scholar
  74. 74.
    Pulla VK, Sriram DS, Soni V, Viswanadha S, Sriram D, Yogeeswari P (2015) Targeting NAMPT for therapeutic intervention in cancer and inflammation: structure-based drug design and biological screening. Chem Biol Drug Des 86(4):881–894PubMedCrossRefGoogle Scholar
  75. 75.
    Rada B, Leto TL (2008) Oxidative innate immune defenses by Nox/Duox family NADPH oxidases. Contrib Microbiol 15:164–187PubMedCentralPubMedCrossRefGoogle Scholar
  76. 76.
    Ren JH, Tao Y, Zhang ZZ, Chen WX, Cai XF, Chen K et al (2014) Sirtuin 1 regulates hepatitis B virus transcription and replication by targeting transcription factor AP-1. J Virol 88:2442–2451PubMedCentralPubMedCrossRefGoogle Scholar
  77. 77.
    Revollo JR, Korner A, Mills KF, Satoh A, Wang T, Garten A et al (2007) Nampt/PBEF/Visfatin regulates insulin secretion in beta cells as a systemic NAD biosynthetic enzyme. Cell Metab 6:363–375PubMedCentralPubMedCrossRefGoogle Scholar
  78. 78.
    Roberts KJ, Cross A, Vasieva O, Moots RJ, Edwards SW (2013) Inhibition of pre-B cell colony-enhancing factor (PBEF/NAMPT/visfatin) decreases the ability of human neutrophils to generate reactive oxidants but does not impair bacterial killing. J Leukoc Biol 94:481–492PubMedCrossRefGoogle Scholar
  79. 79.
    Rodrigues V, Cordeiro-da-Silva A, Laforge M, Ouaissi A, Silvestre R, Estaquier J (2012) Modulation of mammalian apoptotic pathways by intracellular protozoan parasites. Cell Microbiol 14:325–333PubMedCrossRefGoogle Scholar
  80. 80.
    Sampath D, Zabka TS, Misner DL, O’Brien T, Dragovich PS (2015) Inhibition of nicotinamide phosphoribosyltransferase (NAMPT) as a therapeutic strategy in cancer. Pharmacol Ther 151:16–31PubMedCrossRefGoogle Scholar
  81. 81.
    Schmidt SV, Schultze JL (2014) New insights into IDO biology in bacterial and viral infections. Front Immunol 5:384PubMedCentralPubMedCrossRefGoogle Scholar
  82. 82.
    Schreiber V, Dantzer F, Ame JC, de Murcia G (2006) Poly(ADP-ribose): novel functions for an old molecule. Nat Rev Mol Cell Biol 7:517–528PubMedCrossRefGoogle Scholar
  83. 83.
    Schroten H, Spors B, Hucke C, Stins M, Kim KS, Adam R, Daubener W (2001) Potential role of human brain microvascular endothelial cells in the pathogenesis of brain abscess: inhibition of Staphylococcus aureus by activation of indoleamine 2,3-dioxygenase. Neuropediatrics 32:206–210PubMedCrossRefGoogle Scholar
  84. 84.
    Seman M, Adriouch S, Haag F, Koch-Nolte F (2004) Ecto-ADP-ribosyltransferases (ARTs): emerging actors in cell communication and signaling. Curr Med Chem 11:857–872PubMedCrossRefGoogle Scholar
  85. 85.
    Sereno D, Alegre AM, Silvestre R, Vergnes B, Ouaissi A (2005) In vitro antileishmanial activity of nicotinamide. Antimicrob Agents Chemother 49:808–812PubMedCentralPubMedCrossRefGoogle Scholar
  86. 86.
    Shigemura T, Shiohara M, Kato M, Furuta S, Kaneda K, Morishita K et al (2015) Superoxide-generating Nox5alpha is functionally required for the human T-cell leukemia virus Type 1-induced cell transformation phenotype. J Virol 89:9080–9089PubMedCrossRefGoogle Scholar
  87. 87.
    Singh SK, Kurnasov OV, Chen B, Robinson H, Grishin NV, Osterman AL, Zhang H (2002) Crystal structure of Haemophilus influenzae NadR protein. A bifunctional enzyme endowed with NMN adenyltransferase and ribosylnicotinimide kinase activities. J Biol Chem 277:33291–33299PubMedCrossRefGoogle Scholar
  88. 88.
    Siva AC, Bushman F (2002) Poly(ADP-ribose) polymerase 1 is not strictly required for infection of murine cells by retroviruses. J Virol 76:11904–11910PubMedCentralPubMedCrossRefGoogle Scholar
  89. 89.
    Sodhi RK, Singh N, Jaggi AS (2010) Poly(ADP-ribose) polymerase-1 (PARP-1) and its therapeutic implications. Vascul Pharmacol 53:77–87PubMedCrossRefGoogle Scholar
  90. 90.
    Sommer F, Backhed F (2015) The gut microbiota engages different signaling pathways to induce Duox2 expression in the ileum and colon epithelium. Mucosal Immunol 8:372–379PubMedCrossRefGoogle Scholar
  91. 91.
    Sorci L, Kurnasov O, Rodionov D, Osterman A (2010) Genomics and enzymology of NAD biosynthesis. In: Mander L, Liu H-W (eds) Comprehensive natural products II. Elsevier, Oxford, pp 213–257CrossRefGoogle Scholar
  92. 92.
    Strengert M, Jennings R, Davanture S, Hayes P, Gabriel G, Knaus UG (2014) Mucosal reactive oxygen species are required for antiviral response: role of Duox in influenza a virus infection. Antioxid Redox Signal 20:2695–2709PubMedCrossRefGoogle Scholar
  93. 93.
    Sun K, Metzger DW (2014) Influenza infection suppresses NADPH oxidase-dependent phagocytic bacterial clearance and enhances susceptibility to secondary methicillin-resistant Staphylococcus aureus infection. J Immunol 192:3301–3307PubMedCentralPubMedCrossRefGoogle Scholar
  94. 94.
    Takeuchi M, Niimi T, Masumoto M, Orita M, Yokota H, Yamamoto T (2014) Discovery of a novel nicotinamide phosphoribosyl transferase (NAMPT) inhibitor via in silico screening. Biol Pharm Bull 37:31–36PubMedCrossRefGoogle Scholar
  95. 95.
    Tatsuno I, Isaka M, Minami M, Hasegawa T (2010) NADase as a target molecule of in vivo suppression of the toxicity in the invasive M-1 group A Streptococcal isolates. BMC Microbiol 10:144PubMedCentralPubMedCrossRefGoogle Scholar
  96. 96.
    Van Assche T, Deschacht M, da Luz RA, Maes L, Cos P (2011) Leishmania-macrophage interactions: insights into the redox biology. Free Radic Biol Med 51:337–351PubMedCrossRefGoogle Scholar
  97. 97.
    Van den Bergh R, Florence E, Vlieghe E, Boonefaes T, Grooten J, Houthuys E et al (2010) Transcriptome analysis of monocyte-HIV interactions. Retrovirology 7:53PubMedCentralPubMedCrossRefGoogle Scholar
  98. 98.
    Viegas MS, do Carmo A, Silva T, Seco F, Serra V, Lacerda M, Martins TC (2007) CD38 plays a role in effective containment of mycobacteria within granulomata and polarization of Th1 immune responses against Mycobacterium avium. Microbes Infect 9:847–854PubMedCrossRefGoogle Scholar
  99. 99.
    Vilcheze C, Weinrick B, Wong KW, Chen B, Jacobs WR Jr (2010) NAD+ auxotrophy is bacteriocidal for the tubercle bacilli. Mol Microbiol 76:365–377PubMedCentralPubMedCrossRefGoogle Scholar
  100. 100.
    Williamson DH, Lund P, Krebs HA (1967) The redox state of free nicotinamide-adenine dinucleotide in the cytoplasm and mitochondria of rat liver. Biochem J 103:514–527PubMedCentralPubMedCrossRefGoogle Scholar
  101. 101.
    Xie H, Lei N, Gong AY, Chen XM, Hu G (2014) Cryptosporidium parvum induces SIRT1 expression in host epithelial cells through downregulating let-7i. Hum Immunol 75:760–765PubMedCentralPubMedCrossRefGoogle Scholar
  102. 102.
    Yamahira A, Narita M, Iwabuchi M, Uchiyama T, Iwaya S, Ohiwa R et al (2014) Activation of the leukemia plasmacytoid dendritic cell line PMDC05 by Toho-1, a novel IDO inhibitor. Anticancer Res 34:4021–4028PubMedGoogle Scholar
  103. 103.
    Yang H, Yang T, Baur JA, Perez E, Matsui T, Carmona JJ et al (2007) Nutrient-sensitive mitochondrial NAD+ levels dictate cell survival. Cell 130:1095–1107PubMedCentralPubMedCrossRefGoogle Scholar
  104. 104.
    Yu H, Schwarzer K, Forster M, Kniemeyer O, Forsbach-Birk V, Straube E, Rodel J (2010) Role of high-mobility group box 1 protein and poly(ADP-ribose) polymerase 1 degradation in Chlamydia trachomatis-induced cytopathicity. Infect Immun 78:3288–3297PubMedCentralPubMedCrossRefGoogle Scholar
  105. 105.
    Yu JW, Sun LJ, Liu W, Zhao YH, Kang P, Yan BZ (2013) Hepatitis C virus core protein induces hepatic metabolism disorders through down-regulation of the SIRT1-AMPK signaling pathway. Int J Infect Dis 17:e539–e545PubMedCrossRefGoogle Scholar
  106. 106.
    Yu SW, Wang H, Poitras MF, Coombs C, Bowers WJ, Federoff HJ et al (2002) Mediation of poly(ADP-ribose) polymerase-1-dependent cell death by apoptosis-inducing factor. Science 297:259–263PubMedCrossRefGoogle Scholar
  107. 107.
    Zerez CR, Roth EF Jr, Schulman S, Tanaka KR (1990) Increased nicotinamide adenine dinucleotide content and synthesis in Plasmodium falciparum-infected human erythrocytes. Blood 75:1705–1710PubMedGoogle Scholar
  108. 108.
    Zhang YJ, Reddy MC, Ioerger TR, Rothchild AC, Dartois V, Schuster BM et al (2013) Tryptophan biosynthesis protects mycobacteria from CD4 T-cell-mediated killing. Cell 155:1296–1308PubMedCentralPubMedCrossRefGoogle Scholar

Copyright information

© Springer International Publishing 2015

Authors and Affiliations

  • Inês Mesquita
    • 1
    • 2
  • Patrícia Varela
    • 1
    • 2
  • Ana Belinha
    • 1
    • 2
  • Joana Gaifem
    • 1
    • 2
  • Mireille Laforge
    • 4
  • Baptiste Vergnes
    • 3
  • Jérôme Estaquier
    • 4
    • 5
  • Ricardo Silvestre
    • 1
    • 2
  1. 1.Microbiology and Infection Research Domain, Life and Health Sciences Research Institute (ICVS), School of Health SciencesUniversity of MinhoBragaPortugal
  2. 2.ICVS/3B’s-PT Government Associate LaboratoryBraga/GuimarãesPortugal
  3. 3.MIVEGEC (IRD 224-CNRS 5290-Université Montpellier)Institut de Recherche pour le Développement (IRD)MontpellierFrance
  4. 4.CNRS FR 3636Université Paris DescartesParisFrance
  5. 5.Centre de Recherche du CHU de QuébecUniversité LavalQuebecCanada

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