title: IL-10 inhibits mature fibrotic granuloma formation during Mycobacterium tuberculosis infection.
abstract: Protective immunity and latent Mycobacterium tuberculosis infection in humans are associated with the formation of mature protective granulomas within the lung. Unfortunately, understanding the importance of such structures has been hindered by the lack of small-animal models that can develop mature granulomas. In this article, we describe for the first time, to our knowledge, the formation of mature, fibrotic M. tuberculosis-containing pulmonary granulomas in a mouse model of IL-10 deficiency (CBA/J IL-10(-/-)). Long-term control of M. tuberculosis infection in the absence of IL-10 was also associated with an early and enhanced capacity for Ag presentation and a significant increase in the generation of multifunctional T cells. Although IL-10 deficiency is known to enhance Th1 immune responses in general, we demonstrate in this study using transient anti-IL-10R treatment that it is the presence of IL-10 in vivo during the first month of M. tuberculosis infection that plays a definitive role in the inhibition of optimum protective immunity that can establish the environment for mature granuloma formation. Although the importance of IL-10 during M. tuberculosis infection has been debated, our data demonstrate that in CBA/J mice, IL-10 plays a significant early inhibitory role in preventing the development of protective immunity associated with containment of M. tuberculosis infection.
authors: Department of Microbial Infection and Immunity, The Ohio State University, Columbus, OH 43210, USA.
authors: Joshua C
authors: JC
authors: Cyktor
authors: Bridget
authors: B
authors: Carruthers
authors: Rachel A
authors: RA
authors: Kominsky
authors: Gillian L
authors: GL
authors: Beamer
authors: Paul
authors: P
authors: Stromberg
authors: Joanne
authors: J
authors: Turner
mesh_terms: D000818:Animals; D058491:Bacterial Load; D004195:Disease Models, Animal; D005355:Fibrosis / Q000517:prevention & control; D015769:Granuloma, Respiratory Tract / Q000276:immunology* / Q000382:microbiology / Q000517:prevention & control*; D016753:Interleukin-10 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D008168:Lung / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D008198:Lymph Nodes / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D051379:Mice; D008809:Mice, Inbred C3H; D008808:Mice, Inbred CBA; D018345:Mice, Knockout; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D013154:Spleen / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D014397:Tuberculosis, Pulmonary / Q000276:immunology* / Q000382:microbiology / Q000517:prevention & control*
chemical_list: C556062:IL10 protein, mouse; D016753:Interleukin-10
references: N Engl J Med. 1989 Mar 2;320(9):545-50
references: 2915665
references: Am J Pathol. 2009 Jun;174(6):2190-201
references: 19443700
references: J Immunol. 2011 Jun 15;186(12):7110-9
references: 21555529
references: Nat Rev Microbiol. 2007 Jan;5(1):39-47
references: 17160001
references: Mucosal Immunol. 2011 May;4(3):261-70
references: 21451501
references: Clin Exp Immunol. 1998 Jul;113(1):55-8
references: 9697983
references: Eur J Immunol. 2010 Aug;40(8):2139-42
references: 20853500
references: J Exp Med. 2010 Mar 15;207(3):591-605
references: 20212068
references: Am J Respir Cell Mol Biol. 2011 Jul;45(1):172-80
references: 20889800
references: Exp Mol Pathol. 2010 Dec;89(3):327-33
references: 20858486
references: PLoS One. 2009 Jun 16;4(6):e5930
references: 19529771
references: J Pathol. 2006 Jan;208(2):261-9
references: 16362982
references: Clin Vaccine Immunol. 2008 Mar;15(3):474-83
references: 18184822
references: Clin Exp Immunol. 1993 Nov;94(2):322-9
references: 8222323
references: Tuberculosis (Edinb). 2009 Mar;89(2):149-57
references: 19213603
references: Clin Exp Immunol. 1999 Jan;115(1):110-3
references: 9933428
references: J Immunol. 2002 Dec 1;169(11):6343-51
references: 12444141
references: Infect Immun. 2003 Oct;71(10):5845-54
references: 14500506
references: Tuberculosis (Edinb). 2003;83(5):279-85
references: 12972341
references: J Exp Med. 2003 Jan 6;197(1):7-17
references: 12515809
references: Immunology. 1998 Feb;93(2):270-4
references: 9616378
references: Infect Immun. 1993 Aug;61(8):3482-9
references: 8335379
references: J Exp Med. 2001 Dec 17;194(12):1847-59
references: 11748285
references: Immunology. 1999 Jan;96(1):16-21
references: 10233673
references: Infect Immun. 1997 Dec;65(12):5149-56
references: 9393809
references: Immunology. 2003 Jun;109(2):295-9
references: 12757625
references: Infect Immun. 2006 Jun;74(6):3314-24
references: 16714559
references: J Immunol. 2007 Jun 15;178(12):8028-35
references: 17548640
references: Infect Immun. 2001 May;69(5):3264-70
references: 11292749
references: Eur J Immunol. 2008 Feb;38(2):350-63
references: 18200635
references: Eur J Immunol. 2010 Aug;40(8):2200-10
references: 20518032
references: J Exp Med. 1993 Dec 1;178(6):2249-54
references: 7504064
references: PLoS One. 2011 Jan 13;6(1):e16161
references: 21249199
references: J Immunol. 2011 Sep 1;187(5):2222-32
references: 21775682
references: J Exp Med. 1993 Dec 1;178(6):2243-7
references: 8245795
references: Nat Immunol. 2009 Sep;10(9):943-8
references: 19692995
references: Clin Infect Dis. 2005 Aug 1;41 Suppl 3:S189-93
references: 15983898
references: J Immunol. 2012 Oct 15;189(8):4079-87
references: 22972927
references: J Immunol. 2009 Jul 15;183(2):1301-12
references: 19561100
references: EMBO Mol Med. 2010 Jul;2(7):258-74
references: 20597103
references: J Immunol. 2010 Jun 1;184(11):6537-44
references: 20435929
references: J Clin Invest. 2010 Sep;120(9):3365-76
references: 20679732
references: Arch Immunol Ther Exp (Warsz). 2005 Nov-Dec;53(6):469-83
references: 16407780
references: Annu Rev Immunol. 2002;20:581-620
references: 11861613
references: J Exp Med. 2007 Jun 11;204(6):1405-16
references: 17535971
references: J Immunol. 2008 Oct 15;181(8):5545-50
references: 18832712
references: J Immunol. 2005 Apr 1;174(7):4185-92
references: 15778379
references: JAMA. 1999 Aug 18;282(7):677-86
references: 10517722
references: Scand J Immunol. 2001 Jan;53(1):85-91
references: 11169211
references: Infect Immun. 2004 May;72(5):2628-34
references: 15102771
references: Nature. 1998 Jul 30;394(6692):485-90
references: 9697772
references: Annu Rev Microbiol. 2001;55:139-63
references: 11544352
references: J Exp Med. 2008 Jan 21;205(1):105-15
references: 18158321
references: Antimicrob Agents Chemother. 2003 Mar;47(3):833-6
references: 12604509
references: Microbes Infect. 2006 Apr;8(4):1179-88
references: 16513383
references: J Exp Med. 2008 Sep 29;205(10):2359-68
references: 18779346