Alteraciones inflamatorias clínicas y moleculares en enfermedad granulomatosa crónica

Autores/as

DOI:

https://doi.org/10.29262/ram.v67i4.784

Palabras clave:

NADPH oxidasa, inflamación, enfermedad granulomatosa crónica, granulomas, especies reactivas de oxígeno

Resumen

La enfermedad granulomatosa crónica (EGC) es un error innato de la inmunidad. Se caracteriza por deficiencia en la función del complejo de la NADPH oxidasa. La EGC ha sido una oportunidad para estudiar la función de las especies reactivas de oxígeno (ROS) en el sistema inmune innato. La ausencia de ROS producidas por la NADPH oxidasa en los neutrófilos y en los macrófagos lleva a mayor susceptibilidad a infecciones bacterianas y fúngicas, debido a que las ROS participan en la eliminación de los microorganismos. Las manifestaciones inflamatorias y autoinmunes también están presentes en la EGC, sin embargo, no es del todo clara la relación de causalidad entre la falta de ROS y los síntomas inflamatorios. Se han realizado diversos ensayos in vitro en humanos y experimentales en ratones para tratar de entender esta relación. Los estudios muestran que las ROS reaccionan con diferentes moléculas del sistema inmune, inhibiendo o estimulando su función, lo que explica que en la EGC se afecten varias vías de la inflamación que no están relacionadas entre sí; por lo tanto, han sido diversos los mecanismos de afectación descritos, como por ejemplo una mayor producción de citocinas proinflamatorias, un incremento en los linfocitos TH17 y una alteración en procesos como eferocitosis, apoptosis, autofagia e inflamasoma. El entendimiento de los mecanismos que llevan a la inflamación en la deficiencia del complejo de la NADPH oxidasa ha llevado a plantear nuevos tratamientos que actúan en procesos como la autofagia, el inflamosoma o el bloqueo de citocinas proinflamatorias. En esta revisión describimos las diferentes manifestaciones inflamatorias en EGC y los mecanismos moleculares a través de los cuales la falta de ROS conduce a la hiperinflamación.

Citas

BIBLOGRAFÍA

Dahlgren C, Karlsson A, Bylund J. Intracellular Neutrophil Oxidants: From Laboratory Curiosity to Clinical Reality. J Immunol 2019;202:3127-34.

Dinauer MC. Inflammatory consequences of inherited disorders affecting neutrophil function. Blood 2019;133:2130-9.

Buvelot H, Jaquet V, Krause KH. Mammalian NADPH Oxidases. Methods Mol Biol 2019;1982:17-36.

Bustamante J, Arias AA, Vogt G, et al. Germline CYBB mutations that selectively affect macrophages in kindreds with X-linked predisposition to tuberculous mycobacterial disease. Nat Immunol 2011;12:213-21.

Lambeth JD, Neish AS. Nox enzymes and new thinking on reactive oxygen: a double-edged sword revisited. Annu Rev Pathol 2014;9:119-45.

Koga H, Terasawa H, Nunoi H, Takeshige K, Inagaki F, Sumimoto H. Tetratricopeptide repeat (TPR) motifs of p67(phox) participate in interaction with the small GTPase Rac and activation of the phagocyte NADPH oxidase. J Biol Chem 1999;274:25051-60.

Magnani F, Mattevi A. Structure and mechanisms of ROS generation by NADPH oxidases. Curr Opin Struct Biol 2019;59:91-7.

Singel KL, Segal BH. NOX2-dependent regulation of inflammation. Clin Sci (Lond) 2016;130:479-90.

Buck A, Sanchez Klose FP, Venkatakrishnan V, et al. DPI Selectively Inhibits Intracellular NADPH Oxidase Activity in Human Neutrophils. Immunohorizons 2019;3:488-97.

Reshetnikov V, Hahn J, Maueroder C, et al. Chemical Tools for Targeted Amplification of Reactive Oxygen Species in Neutrophils. Front Immunol 2018;9:1827.

Blancas-Galicia L, Santos-Chavez E, Deswarte C, et al. Genetic, Immunological, and Clinical Features of the First Mexican Cohort of Patients with Chronic Granulomatous Disease. J Clin Immunol 2020.

Rosenbaum BE, Shenoy R, Vuppula S, Thomas K, Moy L, Kaul A. Colitis as the Sole Initial Presentation of Chronic Granulomatous Disease: Histopathologic Clues to Diagnosis. Pediatr Infect Dis J 2016;35:1229-31.

Magnani A, Brosselin P, Beaute J, et al. Inflammatory manifestations in a single-center cohort of patients with chronic granulomatous disease. J Allergy Clin Immunol 2014;134:655-62 e8.

Rosenzweig SD. Inflammatory manifestations in chronic granulomatous disease (CGD). J Clin Immunol 2008;28 Suppl 1:S67-72.

Goldblatt D. Recent advances in chronic granulomatous disease. J Infect 2014;69 Suppl 1:S32-5.

Holland SM. Chronic granulomatous disease. Clin Rev Allergy Immunol 2010;38:3-10.

Winkelstein JA, Marino MC, Johnston RB, Jr., et al. Chronic granulomatous disease. Report on a national registry of 368 patients. Medicine (Baltimore) 2000;79:155-69.

Arnold DE, Heimall JR. A Review of Chronic Granulomatous Disease. Adv Ther 2017;34:2543-57.

De Ravin SS, Naumann N, Cowen EW, et al. Chronic granulomatous disease as a risk factor for autoimmune disease. J Allergy Clin Immunol 2008;122:1097-103.

Leiding JW, Holland SM. Chronic Granulomatous Disease. In: Adam MP, Ardinger HH, Pagon RA, et al., eds. GeneReviews((R)). Seattle (WA)1993.

Thomas DC. How the phagocyte NADPH oxidase regulates innate immunity. Free Radic Biol Med 2018;125:44-52.

Lopez-Hernandez I, Guzman-Martinez MN, Medina-Vera I, et al. Clinical Manifestations in Carriers of X-Linked Chronic Granulomatous Disease in Mexico. J Investig Allergol Clin Immunol 2019;29:134-6.

Gennery AR, Albert MH, Slatter MA, Lankester A. Hematopoietic Stem Cell Transplantation for Primary Immunodeficiencies. Front Pediatr 2019;7:445.

Alvarez-Cardona A, Rodriguez-Lozano AL, Blancas-Galicia L, Rivas-Larrauri FE, Yamazaki-Nakashimada MA. Intravenous immunoglobulin treatment for macrophage activation syndrome complicating chronic granulomatous disease. J Clin Immunol 2012;32:207-11.

Kuijpers T, Lutter R. Inflammation and repeated infections in CGD: two sides of a coin. Cell Mol Life Sci 2012;69:7-15.

Freeman AF, Marciano BE, Anderson VL, Uzel G, Costas C, Holland SM. Corticosteroids in the treatment of severe nocardia pneumonia in chronic granulomatous disease. Pediatr Infect Dis J 2011;30:806-8.

Venegas-Montoya E, Sorcia-Ramirez G, Scheffler-Mendoza S, et al. Use of corticosteroids as an alternative to surgical treatment for liver abscesses in chronic granulomatous disease. Pediatr Blood Cancer 2016;63:2254-5.

Noel N, Mahlaoui N, Blanche S, et al. Efficacy and safety of thalidomide in patients with inflammatory manifestations of chronic granulomatous disease: a retrospective case series. J Allergy Clin Immunol 2013;132:997-1000 e1-4.

Gabrion A, Hmitou I, Moshous D, et al. Mammalian target of rapamycin inhibition counterbalances the inflammatory status of immune cells in patients with chronic granulomatous disease. J Allergy Clin Immunol 2017;139:1641-9 e6.

Henriet SS, Jans J, Simonetti E, et al. Chloroquine modulates the fungal immune response in phagocytic cells from patients with chronic granulomatous disease. J Infect Dis 2013;207:1932-9.

Hui X, Liu D, Wang W, et al. Low-Dose Pioglitazone does not Increase ROS Production in Chronic Granulomatous Disease Patients with Severe Infection. J Clin Immunol 2019.

van de Geer A, Nieto-Patlan A, Kuhns DB, et al. Inherited p40phox deficiency differs from classic chronic granulomatous disease. J Clin Invest 2018;128:3957-75.

Matute JD, Arias AA, Wright NA, et al. A new genetic subgroup of chronic granulomatous disease with autosomal recessive mutations in p40 phox and selective defects in neutrophil NADPH oxidase activity. Blood 2009;114:3309-15.

Wright M, Chandrakasan S, Okou DT, et al. Early Onset Granulomatous Colitis Associated with a Mutation in NCF4 Resolved with Hematopoietic Stem Cell Transplantation. J Pediatr 2019;210:220-5.

Conway KL, Goel G, Sokol H, et al. p40phox expression regulates neutrophil recruitment and function during the resolution phase of intestinal inflammation. J Immunol 2012;189:3631-40.

Thomas DC, Charbonnier LM, Schejtman A, et al. EROS/CYBC1 mutations: Decreased NADPH oxidase function and chronic granulomatous disease. J Allergy Clin Immunol 2019;143:782-5 e1.

Arnadottir GA, Norddahl GL, Gudmundsdottir S, et al. A homozygous loss-of-function mutation leading to CYBC1 deficiency causes chronic granulomatous disease. Nat Commun 2018;9:4447.

Dinauer MC. Neutrophil Defects and Diagnosis Disorders of Neutrophil Function: An Overview. Methods Mol Biol 2020;2087:11-29.

Chan TY, Yen CL, Huang YF, et al. Increased ILC3s associated with higher levels of IL-1beta aggravates inflammatory arthritis in mice lacking phagocytic NADPH oxidase. Eur J Immunol 2019;49:2063-73.

Horvath R, Rozkova D, Lastovicka J, et al. Expansion of T helper type 17 lymphocytes in patients with chronic granulomatous disease. Clin Exp Immunol 2011;166:26-33.

Kobayashi SD, Voyich JM, Braughton KR, et al. Gene expression profiling provides insight into the pathophysiology of chronic granulomatous disease. J Immunol 2004;172:636-43.

Petersen JE, Hiran TS, Goebel WS, et al. Enhanced cutaneous inflammatory reactions to Aspergillus fumigatus in a murine model of chronic granulomatous disease. J Invest Dermatol 2002;118:424-9.

Morgenstern DE, Gifford MA, Li LL, Doerschuk CM, Dinauer MC. Absence of respiratory burst in X-linked chronic granulomatous disease mice leads to abnormalities in both host defense and inflammatory response to Aspergillus fumigatus. J Exp Med 1997;185:207-18.

Han W, Li H, Cai J, et al. NADPH oxidase limits lipopolysaccharide-induced lung inflammation and injury in mice through reduction-oxidation regulation of NF-kappaB activity. J Immunol 2013;190:4786-94.

Bylund J, MacDonald KL, Brown KL, et al. Enhanced inflammatory responses of chronic granulomatous disease leukocytes involve ROS-independent activation of NF-kappa B. Eur J Immunol 2007;37:1087-96.

Gazendam RP, van de Geer A, van Hamme JL, et al. Proinflammatory cytokine response toward fungi but not bacteria in chronic granulomatous disease. J Allergy Clin Immunol 2016;138:928-30 e4.

Henriet SS, van de Sande WW, Lee MJ, et al. Decreased Cell Wall Galactosaminogalactan in Aspergillus nidulans Mediates Dysregulated Inflammation in the Chronic Granulomatous Disease Host. J Interferon Cytokine Res 2016;36:488-98.

Weisser M, Demel UM, Stein S, et al. Hyperinflammation in patients with chronic granulomatous disease leads to impairment of hematopoietic stem cell functions. J Allergy Clin Immunol 2016;138:219-28 e9.

Morgan MJ, Liu ZG. Crosstalk of reactive oxygen species and NF-kappaB signaling. Cell Res 2011;21:103-15.

Deffert C, Carnesecchi S, Yuan H, et al. Hyperinflammation of chronic granulomatous disease is abolished by NOX2 reconstitution in macrophages and dendritic cells. J Pathol 2012;228:341-50.

de Luca A, Smeekens SP, Casagrande A, et al. IL-1 receptor blockade restores autophagy and reduces inflammation in chronic granulomatous disease in mice and in humans. Proc Natl Acad Sci U S A 2014;111:3526-31.

Meissner F, Seger RA, Moshous D, Fischer A, Reichenbach J, Zychlinsky A. Inflammasome activation in NADPH oxidase defective mononuclear phagocytes from patients with chronic granulomatous disease. Blood 2010;116:1570-3.

Zeng MY, Miralda I, Armstrong CL, Uriarte SM, Bagaitkar J. The roles of NADPH oxidase in modulating neutrophil effector responses. Mol Oral Microbiol 2019;34:27-38.

Brown JR, Goldblatt D, Buddle J, Morton L, Thrasher AJ. Diminished production of anti-inflammatory mediators during neutrophil apoptosis and macrophage phagocytosis in chronic granulomatous disease (CGD). J Leukoc Biol 2003;73:591-9.

Fernandez-Boyanapalli R, Frasch SC, Riches DW, Vandivier RW, Henson PM, Bratton DL. PPARgamma activation normalizes resolution of acute sterile inflammation in murine chronic granulomatous disease. Blood 2010;116:4512-22.

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2020-12-24 — Actualizado el 2021-02-12

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Inmunología