Modulación de la respuesta inmune por los lipopolisacáridos bacterianos

Gustavo Aldapa-Vega, Rodolfo Pastelín-Palacios, Armando Isibasi, Mario A. Moreno-Eutimio, Constantino López-Macías

Resumen


El lipopolisacárido (LPS) se encuentra abundantemente en la membrana externa de las bacterias gramnegativas y es un potente estimulador de la respuesta inmunitaria. Al ser la molécula predominante en la superficie bacteriana también es la de mayor actividad biológica. La respuesta del sistema inmunitario del hospedero es activada por el reconocimiento molecular del LPS mediante el receptor tipo Toll 4 (TLR4), por lo que está íntimamente ligada a su estructura. Los microorganismos cuentan con sistemas que les permiten controlar la expresión y estructura del LPS, lo cual les es útil para modular la respuesta inmunitaria del hospedero y lograr la infección. Algunos ejemplos incluyen a Helicobacter pylori, Francisella tularensis, Chlamydia trachomatis y varias especies de Salmonella. Altas concentraciones de LPS pueden inducir fiebre, aumento del ritmo cardiaco y dar lugar a choque séptico y la muerte. En concentraciones relativamente bajas, algunos LPS son inmunomoduladores muy activos que pueden inducir la resistencia no específica a los microorganismos invasores. El esclarecimiento de los mecanismos moleculares y celulares involucrados en el reconocimiento del LPS y de sus variantes estructurales permite entender la respuesta inmune innata, la inflamación y la compleja relación hospedero-patógeno, para el desarrollo de nuevos inmunomoduladores y adyuvantes.


Palabras clave


Lipopolisacárido; Receptor tipo toll 4; Inmunomodulación

Texto completo:

PDF HTML PubMed (English)

Referencias


Beutler B, Rietschel ET. Innate immune sensing and its roots: the story of endotoxin. Nat Rev Immunol. 2003;3(2):169-76.

Freudenberg MA, Merlin T, Gumenscheimer M, Kalis C, Landmann R, Galanos C. Role of lipopolysaccharide susceptibility in the innate immune response to Salmonella typhimurium infection: LPS, a primary target for recognition of Gram-negative bacteria. Microbes Infect. 2001;3(14-15):1213-1222.

Medzhitov R, Janeway C Jr. Jr. Innate immune recognition: mechanisms and pathways. Immunol Rev. 2000;173:89-97.

Kawahara K, Seydel U, Matsuura M, Danbara H, Rietschel ET, Zähringer U. Chemical structure of glycosphingolipids isolated from Sphingomonas paucimobilis. FEBS Lett. 1991;292(1-2):107-110.

Raetz CR, Whitfield C. Lipopolysaccharide endotoxins. Annu Rev Biochem. 2002;71:635-700.

Molinaro A, Holst O, Di Lorenzo F, Callaghan M, Nurisso A, D’Errico G, et al. Chemistry of lipid A: at the heart of innate immunity. Chemistry. 2015;21(2):500-519. doi: 10.1002/chem.201403923.

Bainbridge BW, Karimi-Naser L, Reife R, Blethen F, Ernst RK, Darveau RP. Acyl chain specificity of the acyltransferases LpxA and LpxD and substrate availability contribute to lipid A fatty acid heterogeneity in Porphyromonas gingivalis. J Bacteriol. 2008;190(13):4549-4558.

Steimle A, Autenrieth IB, Frick JS. Structure and function: Lipid A modifications in commensals and pathogens. IInt J Med Microbiol. 2016 Mar 5. pii: S1438-4221(16)30016-30019. doi: 10.1016/j.ijmm.2016.03.001.

Caroff M, Karibian D. Structure of bacterial lipopolysaccharides. Carbohydr Res. 2003;338(23):2431-47.

Tobias PS, Soldau K, Ulevitch RJ. Isolation of a lipopolysaccharide-binding acute phase reactant from rabbit serum. J Exp Med. 1986;164(3):777-793.

Wright SD, Ramos RA, Tobias PS, Ulevitch RJ, Mathison JC. CD14, a receptor for complexes of lipopolysaccharide (LPS) and LPS binding protein. Science. 1990;249(4975):1431-1433.

Heppner G, Weiss DW. High susceptibility of strain a mice to endotoxin and endotoxin-red blood cell mixtures. J Bacteriol. 1965;90(3):696-703.

Shimazu R, Akashi S, Ogata H, Nagai Y, Fukudome K, Miyake K, Kimoto M. MD-2, a molecule that confers lipopolysaccharide responsiveness on Toll-like receptor 4. J Exp Med. 1999;189(11):1777-1782.

Jin MS, Lee JO. Structures of TLR-ligand complexes. CCurr Opin Immunol. 2008;20(4):414-419. doi: 10.1016/j.coi.2008.06.002.

Park BS, Song DH, Kim HM, Choi BS, Lee H, Lee JO. The structural basis of lipopolysaccharide recognition by the TLR4-MD-2 complex. Nature. 2009;458(7242):1191-1195. doi: 10.1038/nature07830.

Mata-Haro V, Cekic C, Martin M, Chilton PM, Casella CR, Mitchell TC. The vaccine adjuvant monophosphoryl lipid A as a TRIF-biased agonist of TLR4. Science. 2007;316(5831):1628-1632.

Nahid MA, Satoh M, Chan EK. MicroRNA in TLR signaling and endotoxin tolerance. Cell Mol Immunol. 2011;8(5):388-403. doi: 10.1038/cmi.2011.26.

Zhang M, Liu F, Jia H, Zhang Q, Yin L, Liu W, et al. Inhibition of MicroRNA let-7i depresses maturation and functional state of dendritic cells in response to lipopolysaccharide stimulation via targeting suppressor of cytokine signaling 1. J Immunol. 2011;187(4):1674-1683. doi: 10.4049/jimmunol.1001937.

Nakagawa R, Naka T, Tsutsui H, Fujimoto M, Kimura A, Abe T, et al. SOCS-1 participates in negative regulation of LPS responses. Immunity. 2002;17(5):677-687.

Janssens S, Burns K, Tschopp J, Beyaert R. Regulation of interleukin-1- and lipopolysaccharide-induced NF-kappaB activation by alternative splicing of MyD88. Curr Biol. 2002;12(6):467-471.

Kobayashi K, Hernandez LD, Galán JE, Janeway CA Jr, Medzhitov R, Flavell RA. IRAK-M is a negative regulator of Toll-like receptor signaling. Cell. 2002;110(2):191-202.

Wald D, Qin J, Zhao Z, Qian Y, Naramura M, Tian L, et al. SIGIRR, a negative regulator of Toll-like receptor-interleukin 1 receptor signaling. Nat Immunol. 2003;4(9):920-927.

Gunn JS, Lim KB, Krueger J, Kim K, Guo L, Hackett M, et al. PmrA-PmrB-regulated genes necessary for 4-aminoarabinose lipid A modification and polymyxin resistance. Mol Microbiol. 1998;27(6):1171-1182.

Gunn JS. The Salmonella PmrAB regulon: lipopolysaccharide modifications, antimicrobial peptide resistance and more. Trends Microbiol. 2008;16(6):284-290. doi: 10.1016/j.tim.2008.03.007.

Linehan SA, Holden DW. The interplay between Salmonella typhimurium and its macrophage host--what can it teach us about innate immunity? Immunol Lett. 2003;85(2):183-192.

Eriksson S, Lucchini S, Thompson A, Rhen M, Hinton JC. Unravelling the biology of macrophage infection by gene expression profiling of intracellular Salmonella enterica. Mol Microbiol. 2003;47(1):103-118.

Alpuche Aranda CM1, Swanson JA, Loomis WP, Miller SI. Salmonella typhimurium activates virulence gene transcription within acidified macrophage phagosomes. Proc Natl Acad Sci U S A. 1992;89(21):10079-10083.

Miller SI, Kukral AM, Mekalanos,JJ. A two-component regulatory system (phoP phoQ) controls Salmonella typhimurium virulence. Proc Natl Acad Sci U S A 1989;86(13):5054-5058.

Gunn JS, Hohmann EL, Miller SI. Transcriptional regulation of Salmonella virulence: a PhoQ periplasmic domain mutation results in increased net phosphotransfer to PhoP. J Bacteriol. 1996;178(21):6369-6373.

Guo L, Lim KB, Gunn JS, Bainbridge B, Darveau RP, Hackett M, et al. Regulation of lipid A modifications by Salmonella typhimurium virulence genes phoP-phoQ. Science. 1997;276(5310):250-253.

Gibbons HS, Lin S, Cotter RJ, Raetz CR. Oxygen requirement for the biosynthesis of the S-2-hydroxymyristate moiety in Salmonella typhimurium lipid A. Function of LpxO, A new Fe2+/alpha-ketoglutarate-dependent dioxygenase homologue. J Biol Chem. 2000;275(42):32940-32949.

Kawasaki K, Ernst RK, Miller SI. 3-O-deacylation of lipid A by PagL, a PhoP/PhoQ-regulated deacylase of Salmonella typhimurium, modulates signaling through Toll-like receptor 4. J Biol Chem. 2004;279(19):20044-20048.

Trent MS, Pabich W, Raetz CR, Miller SI. A PhoP/PhoQ-induced Lipase (PagL) that catalyzes 3-O-deacylation of lipid A precursors in membranes of Salmonella typhimurium. J Biol Chem. 2001;276(12):9083-9092.

Guo L, Lim KB, Poduje CM, Daniel M, Gunn JS, Hackett M, et al. Lipid A acylation and bacterial resistance against vertebrate antimicrobial peptides. Cell. 1998;95(2):189-198

Shafer WM, Martin LE, Spitznagel JK. Cationic antimicrobial proteins isolated from human neutrophil granulocytes in the presence of diisopropyl fluorophosphate. Infect Immun. 1984;45(1):29-35.

Roland KL, Martin LE, Esther CR, Spitznagel JK. Spontaneous pmrA mutants of Salmonella typhimurium LT2 define a new two-component regulatory system with a possible role in virulence. J Bacteriol. 1993;175(13):4154-4164.

Gunn JS, Miller SI. PhoP-PhoQ activates transcription of pmrAB, encoding a two-component regulatory system involved in Salmonella typhimurium antimicrobial peptide resistance. J Bacteriol. 1996;178(23):6857-64.

Pastelin-Palacios R, Gil-Cruz C, Pérez-Shibayama CI, Moreno-Eutimio MA, Cervantes-Barragán L, Arriaga-Pizano L, et al. Subversion of innate and adaptive immune activation induced by structurally modified lipopolysaccharide from Salmonella typhimurium. Immunology. 2011;133(4):469-81. doi: 10.1111/j.1365-2567.2011.03459.x.

Kawahara K, Tsukano H, Watanabe H, Lindner B, Matsuura M. Modification of the structure and activity of lipid A in Yersinia pestis lipopolysaccharide by growth temperature. Infect Immun. 2002;70(8):4092-4098.

Vinogradov E, Perry MB, Conlan JW. Structural analysis of Francisella tularensis lipopolysaccharide. Eur J Biochem. 2002;269(24):6112-6118.

Phillips NJ, Schilling B, McLendon MK, Apicella MA, Gibson BW. Novel modification of lipid A of Francisella tularensis. Infect Immun. 2004;72(9):5340-5348.

Salkowski CA, Detore GR, Vogel SN. Lipopolysaccharide and monophosphoryl lipid A differentially regulate interleukin-12, gamma interferon, and interleukin-10 mRNA production in murine macrophages. Infect Immun. 1997;65(8):3239-47. 43.

Thompson BS, Chilton PM, Ward JR, Evans JT, Mitchell TC. The low-toxicity versions of LPS, MPL adjuvant and RC529, are efficient adjuvants for CD4+ T cells. J Leukoc Biol. 2005;78(6):1273-1280.

Ismaili J, Rennesson J, Aksoy E, Vekemans J, Vincart B, Amraoui Z, et al. Monophosphoryl lipid A activates both human dendritic cells and T cells. J Immunol. 2002;168(2):926-932.




DOI: http://dx.doi.org/10.29262/ram.v63i3.207

Enlaces refback

  • No hay ningún enlace refback.