期刊论文详细信息
BMC Pulmonary Medicine
Immune response to Propionibacterium acnes in patients with sarcoidosis – in vivo and in vitro
Antje Prasse5  Marina A Freudenberg3  Joachim Müller-Quernheim4  Peggy Engelhard2  Niklas Lützen1  Sandrine Tchaptchet3  Jonas Christian Schupp4 
[1]Department of Radiology, University Medical Centre, Freiburg, Germany
[2]Faculty of Biology, University of Freiburg, Freiburg, Germany
[3]Department of Developmental Immunology, Max Planck Institute of Immunobiology und Epigenetics, Freiburg, Germany
[4]Department of Pneumology, University Medical Centre, Albert-Ludwigs University, Killianstr. 5, Freiburg, 79106, Germany
[5]Department of Pneumology, Medical School, Hannover, Germany
关键词: Immune response;    Immunoglobulin;    Propionibacterium acnes;    human;    Sarcoidosis;   
Others  :  1222577
DOI  :  10.1186/s12890-015-0070-7
 received in 2015-03-30, accepted in 2015-07-06,  发布年份 2015
PDF
【 摘 要 】

Background

Propionibacterium acnes was found in lungs and lymph nodes of patients with sarcoidosis and may induce hypersensitivity type granuloma formation. Data regarding the immune response to P. acnes of European sarcoid patients are scarce.

Methods

We assessed the total IgG and IgA amount and specific antibodies to P. acnes and to Staphylococcus aureus, serving as a control, in BAL fluid of 64 patients with sarcoidosis and of 21 healthy volunteers. In a subcohort of sarcoid patients and controls, TNF-α and GM-CSF production of BAL cells stimulated with heat-killed P. acnes were measured.

Results

In sarcoid patients, the total IgG and IgA levels in BAL fluid were significantly elevated compared to healthy volunteers. IgG and IgA titres against P. acnes and S. aureus were increased in sarcoid patients, yet based on the total amount of antibodies, only antibodies directed against P. acnes were relatively and significantly increased. Furthermore, BAL cells of sarcoid patients produced significantly more TNF-α and GM-CSF upon stimulation with heat-killed P. acnes compared to controls.

Conclusions

Patients with sarcoidosis had elevated levels of specific antibodies against P. acnes which suggest contact with this bacterium in the past. Furthermore, BAL cells of sarcoid patients produced inflammatory cytokines (TNF-α and GM-CSF) upon stimulation with P. acnes indicating potential involvement of this pathogen in the pathogenesis of sarcoidosis in some patients.

【 授权许可】

   
2015 Schupp et al.

【 预 览 】
附件列表
Files Size Format View
20150823062232108.pdf 522KB PDF download
Fig. 3. 17KB Image download
Fig. 2. 19KB Image download
Fig. 1. 17KB Image download
【 图 表 】

Fig. 1.

Fig. 2.

Fig. 3.

【 参考文献 】
  • [1]Zissel G. Cellular activation in the immune response of sarcoidosis. Semin Respir Crit Care Med. 2014; 35:307-15.
  • [2]Moller DR. Potential etiologic agents in sarcoidosis. Proc Am Thorac Soc. 2007; 4:465-8.
  • [3]Eishi Y. Etiologic aspect of sarcoidosis as an allergic endogenous infection caused by Propionibacterium acnes. Biomed Res Int. 2013; 2013:935289.
  • [4]Valeyre D, Prasse A, Nunes H, Uzunhan Y, Brillet P-Y, Müller-Quernheim J. Sarcoidosis. Lancet. 2014; 383:1155-67.
  • [5]Ishige I, Usui Y, Takemura T, Eishi Y. Quantitative PCR of mycobacterial and propionibacterial DNA in lymph nodes of Japanese patients with sarcoidosis. Lancet. 1999; 354:120-3.
  • [6]Chen ES, Wahlström J, Song Z, Willett MH, Wikén M, Yung RC, West EE, Mcdyer JF, Zhang Y, Eklund A, Grunewald J, Moller DR. T cell responses to mycobacterial catalase-peroxidase profile a pathogenic antigen in systemic sarcoidosis. J Immunol. 2008; 181:8784-96.
  • [7]Nakata Y, Kataoka M, Ejiri T, Mori Y, Hioka T, Maeda T, Hosoya S, Ohnoshi T, Kimura I. The response of alveolar lymphocytes induced by Propionibacterium acnes in pulmonary sarcoidosis: correlation with clinical studies, pulmonary function studies and bronchoalveolar lavage. Nihon Kyobu Shikkan Gakkai Zasshi. 1989; 27:837-41.
  • [8]Carlisle J, Evans W, Hajizadeh R, Nadaf M, Shepherd B, Ott RD, Richter K, Drake W. Multiple Mycobacterium antigens induce interferon-gamma production from sarcoidosis peripheral blood mononuclear cells. Clin Exp Immunol. 2007; 150:460-8.
  • [9]Orme IM, Andersen P, Boom WH. T cell response to Mycobacterium tuberculosis. J Infect Dis. 1993; 167:1481-97.
  • [10]Ishige I, Eishi Y, Takemura T, Kobayashi I, Nakata K, Tanaka I, Nagaoka S, Iwai K, Watanabe K, Takizawa T, Koike M. Propionibacterium acnes is the most common bacterium commensal in peripheral lung tissue and mediastinal lymph nodes from subjects without sarcoidosis. Sarcoidosis Vasc Diffuse Lung Dis. 2005; 22:33-42.
  • [11]Scott MT, Milas L. The distribution and persistence in vivo of Corynebacterium parvum in relation to its antitumor activity. Cancer Res. 1977; 37:1673-9.
  • [12]Homma JY, Abe C, Chosa H, Ueda K, Saegusa J, Nakayama M, Homma H, Washizaki M, Okano H. Bacteriological investigation on biopsy specimens from patients with sarcoidosis. Jpn J Exp Med. 1978; 48:251-5.
  • [13]Hiramatsu J, Kataoka M, Nakata Y, Okazaki K, Tada S, Tanimoto M, Eishi Y. Propionibacterium acnes DNA detected in bronchoalveolar lavage cells from patients with sarcoidosis. Sarcoidosis Vasc Diffuse Lung Dis. 2003; 20:197-203.
  • [14]Ichikawa H, Kataoka M, Hiramatsu J, Ohmori M, Tanimoto Y, Kanehiro A, Nakata Y, Tanimoto M. Quantitative analysis of propionibacterial DNA in bronchoalveolar lavage cells from patients with sarcoidosis. Sarcoidosis Vasc Diffuse Lung Dis. 2008; 25:15-20.
  • [15]Negi M, Takemura T, Guzman J, Uchida K, Furukawa A, Suzuki Y, Iida T, Ishige I, Minami J, Yamada T, Kawachi H, Costabel U, Eishi Y. Localization of propionibacterium acnes in granulomas supports a possible etiologic link between sarcoidosis and the bacterium. Mod Pathol. 2012; 25:1284-97.
  • [16]Eishi Y, Suga M, Ishige I, Kobayashi D, Yamada T, Takemura T, Takizawa T, Koike M, Kudoh S, Costabel U, Guzman J, Rizzato G, Gambacorta M, du Bois R, Nicholson AG, Sharma OP, Ando M. Quantitative analysis of mycobacterial and propionibacterial DNA in lymph nodes of Japanese and European patients with sarcoidosis. J Clin Microbiol. 2002; 40:198-204.
  • [17]Ebe Y, Ikushima S, Yamaguchi T, Kohno K, Azuma A, Sato K, Ishige I, Usui Y, Takemura T, Eishi Y. Proliferative response of peripheral blood mononuclear cells and levels of antibody to recombinant protein from Propionibacterium acnes DNA expression library in Japanese patients with sarcoidosis. Sarcoidosis Vasc Diffuse Lung Dis. 2000; 17:256-65.
  • [18]Nishiwaki T, Yoneyama H, Eishi Y, Matsuo N, Tatsumi K, Kimura H, Kuriyama T, Matsushima K. Indigenous pulmonary Propionibacterium acnes primes the host in the development of sarcoid-like pulmonary granulomatosis in mice. Am J Pathol. 2004; 165:631-9.
  • [19]McCaskill JG, Chason KD, Hua X, Neuringer IP, Ghio AJ, Funkhouser WK, Tilley SL. Pulmonary immune responses to Propionibacterium acnes in C57BL/6 and BALB/c mice. Am J Respir Cell Mol Biol. 2006; 35:347-56.
  • [20]Iio K, Iio TU, Okui Y, Ichikawa H, Tanimoto Y, Miyahara N, Kanehiro A, Tanimoto M, Nakata Y, Kataoka M. Experimental pulmonary granuloma mimicking sarcoidosis induced by Propionibacterium acnes in mice. Acta Med Okayama. 2010; 64:75-83.
  • [21]Tchaptchet S, Gumenscheimer M, Kalis C, Freudenberg N, Hölscher C, Kirschning CJ, Lamers M, Galanos C, Freudenberg MA. TLR9-dependent and independent pathways drive activation of the immune system by Propionibacterium acnes. PLoS One. 2012; 7: Article ID e39155
  • [22]Ziegenhagen MW, Schrum S, Zissel G, Zipfel PF, Schlaak M, Müller-Quernheim J. Increased expression of proinflammatory chemokines in bronchoalveolar lavage cells of patients with progressing idiopathic pulmonary fibrosis and sarcoidosis. J Investig Med. 1998; 46:223-31.
  • [23]Smith D, Hänsch H, Bancroft G, Ehlers S. T-cell-independent granuloma formation in response to Mycobacterium avium: role of tumour necrosis factor-alpha and interferon-gamma. Immunology. 1997; 92:413-21.
  • [24]Broos CE, van Nimwegen M, Hoogsteden HC, Hendriks RW, Kool M, van den Blink B. Granuloma Formation in Pulmonary Sarcoidosis. Front Immunol. 2013; 4:437.
  • [25]Lemaire I, Yang H, Lauzon W, Gendron N. M-CSF and GM-CSF promote alveolar macrophage differentiation into multinucleated giant cells with distinct phenotypes. J Leukoc Biol. 1996; 60:509-18.
  • [26]Prasse A, Pechkovsky DV, Toews GB, Jungraithmayr W, Kollert F, Goldmann T, Vollmer E, Müller-Quernheim J, Zissel G. A vicious circle of alveolar macrophages and fibroblasts perpetuates pulmonary fibrosis via CCL18. Am J Respir Crit Care Med. 2006; 173:781-92.
  • [27]Sing A, Merlin T, Knopf HP, Nielsen PJ, Loppnow H, Galanos C, Freudenberg MA. Bacterial induction of beta interferon in mice is a function of the lipopolysaccharide component. Infect Immun. 2000; 68:1600-7.
  • [28]Vandenplas O, Depelchin S, Delaunois L, Delwiche JP, Sibille Y. Bronchoalveolar lavage immunoglobulin A and G and antiproteases correlate with changes in diffusion indices during the natural course of pulmonary sarcoidosis. Eur Respir J. 1994; 7:1856-64.
  • [29]Snapper CM, Rosas F, Moorman MA, Jin L, Shanebeck K, Klinman DM, Kehry MR, Mond JJ, Maliszewski CR. IFN-gamma is a potent inducer of Ig secretion by sort-purified murine B cells activated through the mIg, but not the CD40, signaling pathway. Int Immunol. 1996; 8:877-85.
  • [30]Hunninghake GW, Crystal RG. Mechanisms of hypergammaglobulinemia in pulmonary sarcoidosis. Site of increased antibody production and role of T lymphocytes. J Clin Invest. 1981; 67:86-92.
  • [31]Rankin JA, Naegel GP, Schrader CE, Matthay RA, Reynolds HY. Air-space immunoglobulin production and levels in bronchoalveolar lavage fluid of normal subjects and patients with sarcoidosis. Am Rev Respir Dis. 1983; 127:442-8.
  • [32]Grunewald J, Eklund A, Wigzell H, Van Meijgaarden KE, Ottenhoff TH. Bronchoalveolar lavage cells from sarcoidosis patients and healthy controls can efficiently present antigens. J Intern Med. 1999; 245:353-7.
  • [33]Robinson J. Colonization and infection of the respiratory tract: What do we know? Paediatr Child Health. 2004; 9:21-4.
  • [34]Janeway CJ, Travers P, Walport M, Shlomchik M: The distribution and functions of immunoglobulin isotypes. In Immunobiology: The Immune System in Health and Disease. 5th edition. Garland Science; 2001.
  • [35]Goronzy JJ, Weyand CM. Understanding immunosenescence to improve responses to vaccines. Nat Immunol. 2013; 14(April):428-36.
  • [36]Müller-Quernheim J, Pfeifer S, Männel D, Strausz J, Ferlinz R. Lung-restricted activation of the alveolar macrophage/monocyte system in pulmonary sarcoidosis. Am Rev Respir Dis. 1992; 145:187-92.
  • [37]Baughman RP, Strohofer SA, Buchsbaum J, Lower EE. Release of tumor necrosis factor by alveolar macrophages of patients with sarcoidosis. J Lab Clin Med. 1990; 115:36-42.
  • [38]Prior C, Knight RA, Herold M, Ott G, Spiteri MA. Pulmonary sarcoidosis: patterns of cytokine release in vitro. Eur Respir J. 1996; 9:47-53.
  • [39]Mori Y, Nakata Y, Kataoka M, Ejiri T, Hioka T, Maeda T, Hosoya S, Ohnoshi T, Kimura I. Interleukin-2 production and receptor expression of alveolar lymphocytes stimulated by Propionibacterium acnes in sarcoidosis. Nihon Kyobu Shikkan Gakkai Zasshi. 1989; 27:42-50.
  • [40]Jasson F, Nagy I, Knol AC, Zuliani T, Khammari A, Dréno B. Different strains of Propionibacterium acnes modulate differently the cutaneous innate immunity. Exp Dermatol. 2013; 22:587-92.
  • [41]Chen ES, Moller DR. Etiologic role of infectious agents. Semin Respir Crit Care Med. 2014; 35:285-95.
  • [42]Scadding JG. Prognosis of intrathoracic sarcoidosis in England. A review of 136 cases after five years’ observation. Br Med J. 1961; 2:1165-72.
  文献评价指标  
  下载次数:30次 浏览次数:33次