title: Virulence and immune response induced by Mycobacterium avium complex strains in a model of progressive pulmonary tuberculosis and subcutaneous infection in BALB/c mice.
abstract: The genus Mycobacterium comprises more than 150 species, including important pathogens for humans which cause major public health problems. The vast majority of efforts to understand the genus have been addressed in studies with Mycobacterium tuberculosis. The biological differentiation between M. tuberculosis and nontuberculous mycobacteria (NTM) is important because there are distinctions in the sources of infection, treatments, and the course of disease. Likewise, the importance of studying NTM is not only due to its clinical significance but also due to the mechanisms by which some species are pathogenic while others are not. Mycobacterium avium complex (MAC) is the most important group of NTM opportunistic pathogens, since it is the second largest medical complex in the genus after the M. tuberculosis complex. Here, we evaluated the virulence and immune response of M. avium subsp. avium and Mycobacterium colombiense, using experimental models of progressive pulmonary tuberculosis and subcutaneous infection in BALB/c mice. Mice infected intratracheally with a high dose of MAC strains showed high expression of tumor necrosis factor alpha (TNF-α) and inducible nitric oxide synthase with rapid bacillus elimination and numerous granulomas, but without lung consolidation during late infection in coexistence with high expression of anti-inflammatory cytokines. In contrast, subcutaneous infection showed high production of the proinflammatory cytokines TNF-α and gamma interferon with relatively low production of anti-inflammatory cytokines such as interleukin-10 (IL-10) or IL-4, which efficiently eliminate the bacilli but maintain extensive inflammation and fibrosis. Thus, MAC infection evokes different immune and inflammatory responses depending on the MAC species and affected tissue.
authors: Department of Microbiology, Medicine School, National University of Colombia, Bogotá, Colombia.
authors: Mónica
authors: M
authors: González-Pérez
authors: Leonardo
authors: L
authors: Mariño-Ramírez
authors: Carlos Alberto
authors: CA
authors: Parra-López
authors: Martha Isabel
authors: MI
authors: Murcia
authors: Brenda
authors: B
authors: Marquina
authors: Dulce
authors: D
authors: Mata-Espinoza
authors: Yadira
authors: Y
authors: Rodriguez-Míguez
authors: Guillermina J
authors: GJ
authors: Baay-Guzman
authors: Sara
authors: S
authors: Huerta-Yepez
authors: Rogelio
authors: R
authors: Hernandez-Pando
mesh_terms: D000818:Animals; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D006801:Humans; D008168:Lung / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009164:Mycobacterium Infections / Q000276:immunology* / Q000382:microbiology; D015269:Mycobacterium avium Complex / Q000276:immunology* / Q000472:pathogenicity*; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis; D012867:Skin / Q000473:pathology; D014382:Tuberculosis, Cutaneous / Q000276:immunology* / Q000382:microbiology; D014397:Tuberculosis, Pulmonary / Q000276:immunology* / Q000382:microbiology
chemical_list: D016207:Cytokines; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse
references: Immunology. 2001 Jul;103(3):368-74
references: 11454066
references: Nature. 1999 Nov 4;402(6757):79-83
references: 10573420
references: Int J Clin Pract. 2008 Dec;62(12):1947-55
references: 19166441
references: Scand J Immunol. 1999 Aug;50(2):127-36
references: 10447916
references: Mol Microbiol. 1999 Oct;34(2):257-67
references: 10564470
references: J Biol Chem. 2004 Oct 8;279(41):42584-92
references: 15292265
references: J Clin Microbiol. 2008 May;46(5):1885-7
references: 18305134
references: Immunology. 1996 Sep;89(1):26-33
references: 8911136
references: Clin Chest Med. 2002 Sep;23(3):553-67
references: 12370992
references: Eur J Clin Microbiol Infect Dis. 2009 Jul;28(7):739-44
references: 19219472
references: Immunol Res. 2006;35(3):179-90
references: 17172645
references: Infect Immun. 1995 Oct;63(10):3759-64
references: 7558277
references: Cell Mol Life Sci. 2001 Dec;58(14):2018-42
references: 11814054
references: Microbes Infect. 2008 Jul;10(9):968-72
references: 18662796
references: Clin Microbiol Infect. 2013 Jan;19(1):91-96
references: 22439981
references: Clin Exp Immunol. 2009 Aug;157(2):271-81
references: 19604267
references: Microbiology (Reading). 2010 Mar;156(Pt 3):687-694
references: 19926652
references: Eur Respir J. 2004 May;23(5):741-6
references: 15176690
references: BMC Infect Dis. 2001;1:21
references: 11722797
references: N Z Med J. 2007 Jun 15;120(1256):U2580
references: 17589548
references: J Dermatol. 1998 Jun;25(6):384-90
references: 9675346
references: Am J Respir Crit Care Med. 2007 Feb 15;175(4):367-416
references: 17277290
references: Int J Syst Evol Microbiol. 2009 Sep;59(Pt 9):2277-82
references: 19620376
references: Microbes Infect. 2006 Jul;8(8):2245-53
references: 16782391
references: Int J Tuberc Lung Dis. 2011 Apr;15(4):447-52
references: 21396201
references: Cell Microbiol. 2004 Mar;6(3):277-87
references: 14764111
references: Mem Inst Oswaldo Cruz. 2006 Nov;101(7):697-714
references: 17160276
references: Int J Exp Pathol. 2006 Aug;87(4):307-15
references: 16875496
references: Scand J Immunol. 2001 Jul-Aug;54(1-2):163-70
references: 11439163
references: Immunology. 2009 Sep;128(1):123-33
references: 19191912
references: Clin Infect Dis. 1995 Aug;21 Suppl 1:S72-6
references: 8547516
references: J Med Case Rep. 2011 Sep 22;5:473
references: 21939536
references: Commun Dis Intell Q Rep. 2003;27(2):180-9
references: 12926733
references: Am J Respir Crit Care Med. 2007 Aug 1;176(3):306-13
references: 17507546
references: Clin Microbiol Rev. 1993 Jul;6(3):266-310
references: 8358707
references: Nucleic Acids Res. 2005 Jan 1;33(Database issue):D325-8
references: 15608208
references: Int J Syst Evol Microbiol. 2006 Sep;56(Pt 9):2049-2054
references: 16957098
references: Int J Syst Evol Microbiol. 2009 Nov;59(Pt 11):2803-8
references: 19628609
references: Thorax. 2007 Aug;62(8):661-6
references: 17311842
references: Annu Rev Microbiol. 2010;64:293-311
references: 20825351
references: Infect Immun. 2012 Apr;80(4):1381-9
references: 22290144
references: Prog Lipid Res. 2005 Sep;44(5):259-302
references: 16115688
references: Immunology. 2006 May;118(1):122-30
references: 16630029
references: Clin Exp Immunol. 2003 Jul;133(1):30-7
references: 12823275
references: Int J Syst Bacteriol. 1997 Apr;47(2):590-2
references: 9103655
references: J Biol Chem. 2002 Oct 11;277(41):38148-58
references: 12138124
references: Infect Immun. 1995 Jun;63(6):2282-7
references: 7768610
references: J Gen Microbiol. 1988 Jul;134(7):2049-55
references: 3149973
references: Am J Med Sci. 2009 Mar;337(3):182-4
references: 19301453
references: PLoS One. 2009 Jul 16;4(7):e6263
references: 19606228
references: Nucleic Acids Res. 2008 Jan;36(Database issue):D539-42
references: 17984080
references: AIDS Res Hum Retroviruses. 1994 Aug;10(8):913-6
references: 7811542
references: Infect Immun. 2002 Dec;70(12):6672-9
references: 12438341
references: Clin Microbiol Rev. 2004 Jan;17(1):98-106
references: 14726457
references: Nucleic Acids Res. 2012 Jan;40(Database issue):D641-5
references: 22067448
references: Infect Immun. 1992 Oct;60(10):4410-3
references: 1398951
references: J Immunol. 1997 May 15;158(10):4822-31
references: 9144497
references: Postgrad Med. 2008 Nov;120(4):78-86
references: 19020369
references: Emerg Infect Dis. 2009 Apr;15(4):619-20
references: 19331753
references: Clin Chest Med. 2002 Sep;23(3):569-83
references: 12370993
references: Chest. 2006 Jun;129(6):1653-72
references: 16778288