• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Logo of envhperEnvironmental Health PerspectivesBrowse ArticlesAbout EHPGeneral InformationAuthorsMediaProgramsPartnerships
Environ Health Perspect. Nov 2002; 110(11): 1119–1125.
PMCID: PMC1241068
Research Article

Mycobacterium terrae isolated from indoor air of a moisture-damaged building induces sustained biphasic inflammatory response in mouse lungs.

Abstract

Occupants in moisture-damaged buildings suffer frequently from respiratory symptoms. This may be partly due to the presence of abnormal microbial growth or the altered microbial flora in the damaged buildings. However, the specific effects of the microbes on respiratory health and the way they provoke clinical manifestations are poorly understood. In the present study, we exposed mice via intratracheal instillation to a single dose of Mycobacterium terrae isolated from the indoor air of a moisture-damaged building (1 X 10(7), 5 X 10(7), or 1 X 10(8) microbes). Inflammation and toxicity in lungs were evaluated 2 hr later. The time course of the effects was assessed with the dose of 1 X 10(8) bacterial cells for up to 28 days. M. terrae caused a sustained biphasic inflammation in mouse lungs. The characteristic features for the first phase, which lasted from 6 hr to 3 days, were elevated proinflammatory cytokine [i.e., tumor necrosis factor alpha (TNF-alpha) and interleukin-6 (IL-6)] levels in the bronchoalveolar lavage fluid (BALF). TNF-alpha was produced in the lungs more intensively than was IL-6. Neutrophils were the most abundant cells in the airways during the first phase, although their numbers in BALF remained elevated up to 21 days. The characteristics of the second phase, which lasted from 7 to 28 days, were elevated TNF-alpha levels in BALF, expression of inducible nitric oxide synthase in BAL cells, and recruitment of mononuclear cells such as lymphocytes and macrophages into the airways. Moreover, total protein, albumin, and lactate dehydrogenase concentrations were elevated in both phases in BALF. The bacteria were detected in lungs up to 28 days. In summary, these observations indicate that M. terrae is capable of provoking a sustained, biphasic inflammation in mouse lungs and can cause a moderate degree of cytotoxicity. Thus, M. terrae can be considered a species with potential to adversely affect the health of the occupants of moisture-damaged buildings.

Full Text

The Full Text of this article is available as a PDF (1.2M).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Andersson MA, Nikulin M, Köljalg U, Andersson MC, Rainey F, Reijula K, Hintikka EL, Salkinoja-Salonen M. Bacteria, molds, and toxins in water-damaged building materials. Appl Environ Microbiol. 1997 Feb;63(2):387–393. [PMC free article] [PubMed]
  • Asano K, Chee CB, Gaston B, Lilly CM, Gerard C, Drazen JM, Stamler JS. Constitutive and inducible nitric oxide synthase gene expression, regulation, and activity in human lung epithelial cells. Proc Natl Acad Sci U S A. 1994 Oct 11;91(21):10089–10093. [PMC free article] [PubMed]
  • Barnes PJ, Chung KF, Page CP. Inflammatory mediators of asthma: an update. Pharmacol Rev. 1998 Dec;50(4):515–596. [PubMed]
  • Brunekreef B. Damp housing and adult respiratory symptoms. Allergy. 1992 Oct;47(5):498–502. [PubMed]
  • Cassatella MA. The production of cytokines by polymorphonuclear neutrophils. Immunol Today. 1995 Jan;16(1):21–26. [PubMed]
  • Chatterjee D, Khoo KH. Mycobacterial lipoarabinomannan: an extraordinary lipoheteroglycan with profound physiological effects. Glycobiology. 1998 Feb;8(2):113–120. [PubMed]
  • Clancy RM, Abramson SB. Nitric oxide: a novel mediator of inflammation. Proc Soc Exp Biol Med. 1995 Nov;210(2):93–101. [PubMed]
  • Cunha FQ, Assreuy J, Moss DW, Rees D, Leal LM, Moncada S, Carrier M, O'Donnell CA, Liew FY. Differential induction of nitric oxide synthase in various organs of the mouse during endotoxaemia: role of TNF-alpha and IL-1-beta. Immunology. 1994 Feb;81(2):211–215. [PMC free article] [PubMed]
  • Dearborn DG, Yike I, Sorenson WG, Miller MJ, Etzel RA. Overview of investigations into pulmonary hemorrhage among infants in Cleveland, Ohio. Environ Health Perspect. 1999 Jun;107 (Suppl 3):495–499. [PMC free article] [PubMed]
  • Denis M. Interferon-gamma-treated murine macrophages inhibit growth of tubercle bacilli via the generation of reactive nitrogen intermediates. Cell Immunol. 1991 Jan;132(1):150–157. [PubMed]
  • Donaldson K. Nonneoplastic lung responses induced in experimental animals by exposure to poorly soluble nonfibrous particles. Inhal Toxicol. 2000 Jan-Feb;12(1-2):121–139. [PubMed]
  • Flappan SM, Portnoy J, Jones P, Barnes C. Infant pulmonary hemorrhage in a suburban home with water damage and mold (Stachybotrys atra). Environ Health Perspect. 1999 Nov;107(11):927–930. [PMC free article] [PubMed]
  • Flesch IE, Kaufmann SH. Mechanisms involved in mycobacterial growth inhibition by gamma interferon-activated bone marrow macrophages: role of reactive nitrogen intermediates. Infect Immun. 1991 Sep;59(9):3213–3218. [PMC free article] [PubMed]
  • Fulton SA, Martin TD, Redline RW, Henry Boom W. Pulmonary immune responses during primary mycobacterium bovis- Calmette-Guerin bacillus infection in C57Bl/6 mice. Am J Respir Cell Mol Biol. 2000 Mar;22(3):333–343. [PubMed]
  • Hagmann M. Public health. A mold's toxic legacy revisited. Science. 2000 Apr 14;288(5464):243–244. [PubMed]
  • Hibbs JB, Jr, Taintor RR, Vavrin Z. Macrophage cytotoxicity: role for L-arginine deiminase and imino nitrogen oxidation to nitrite. Science. 1987 Jan 23;235(4787):473–476. [PubMed]
  • Hobbie JE, Daley RJ, Jasper S. Use of nuclepore filters for counting bacteria by fluorescence microscopy. Appl Environ Microbiol. 1977 May;33(5):1225–1228. [PMC free article] [PubMed]
  • Holland SM. Host defense against nontuberculous mycobacterial infections. Semin Respir Infect. 1996 Dec;11(4):217–230. [PubMed]
  • Huttunen K, Jussila J, Hirvonen MR, Iivanainen E, Katila ML. Comparison of mycobacteria-induced cytotoxicity and inflammatory responses in human and mouse cell lines. Inhal Toxicol. 2001 Nov;13(11):977–991. [PubMed]
  • Huttunen K, Ruotsalainen M, Iivanainen E, Torkko P, Katila M, Hirvonen M. Inflammatory responses in RAW264.7 macrophages caused by mycobacteria isolated from moldy houses. Environ Toxicol Pharmacol. 2000 Jun 1;8(4):237–244. [PubMed]
  • Jablonska E, Jablonski J, Holownia A. Role of neutrophils in release of some cytokines and their soluble receptors. Immunol Lett. 1999 Dec 1;70(3):191–197. [PubMed]
  • Jones GS, Amirault HJ, Andersen BR. Killing of Mycobacterium tuberculosis by neutrophils: a nonoxidative process. J Infect Dis. 1990 Sep;162(3):700–704. [PubMed]
  • Jorens PG, Vermeire PA, Herman AG. L-arginine-dependent nitric oxide synthase: a new metabolic pathway in the lung and airways. Eur Respir J. 1993 Feb;6(2):258–266. [PubMed]
  • Jussila J, Komulainen H, Huttunen K, Roponen M, Hälinen A, Hyvärinen A, Kosma VM, Pelkonen J, Hirvonen MR. Inflammatory responses in mice after intratracheal instillation of spores of Streptomyces californicus isolated from indoor air of a moldy building. Toxicol Appl Pharmacol. 2001 Feb 15;171(1):61–69. [PubMed]
  • Katila ML, Mäntyjärvi RA. Acridine orange staining of smears for demonstration of Mycobacterium tuberculosis. Eur J Clin Microbiol. 1982 Dec;1(6):351–353. [PubMed]
  • Kolb H, Kolb-Bachofen V. Nitric oxide: a pathogenetic factor in autoimmunity. Immunol Today. 1992 May;13(5):157–160. [PubMed]
  • Kopf M, Baumann H, Freer G, Freudenberg M, Lamers M, Kishimoto T, Zinkernagel R, Bluethmann H, Köhler G. Impaired immune and acute-phase responses in interleukin-6-deficient mice. Nature. 1994 Mar 24;368(6469):339–342. [PubMed]
  • Koskinen OM, Husman TM, Meklin TM, Nevalainen AI. The relationship between moisture or mould observations in houses and the state of health of their occupants. Eur Respir J. 1999 Dec;14(6):1363–1367. [PubMed]
  • Krisher KK, Kallay MC, Nolte FS. Primary pulmonary infection caused by Mycobacterium terrae complex. Diagn Microbiol Infect Dis. 1988 Nov;11(3):171–175. [PubMed]
  • Kristof AS, Goldberg P, Laubach V, Hussain SN. Role of inducible nitric oxide synthase in endotoxin-induced acute lung injury. Am J Respir Crit Care Med. 1998 Dec;158(6):1883–1889. [PubMed]
  • Kuze F, Mitsuoka A, Chiba W, Shimizu Y, Ito M, Teramatsu T, Maekawa N, Suzuki Y. Chronic pulmonary infection caused by Mycobacterium terrae complex: a resected case. Am Rev Respir Dis. 1983 Sep;128(3):561–565. [PubMed]
  • Li XY, Brown D, Smith S, MacNee W, Donaldson K. Short-term inflammatory responses following intratracheal instillation of fine and ultrafine carbon black in rats. Inhal Toxicol. 1999 Aug;11(8):709–731. [PubMed]
  • Li XY, Donaldson K, Brown D, MacNee W. The role of tumor necrosis factor in increased airspace epithelial permeability in acute lung inflammation. Am J Respir Cell Mol Biol. 1995 Aug;13(2):185–195. [PubMed]
  • Marshall BG, Chambers MA, Wangoo A, Shaw RJ, Young DB. Production of tumor necrosis factor and nitric oxide by macrophages infected with live and dead mycobacteria and their suppression by an interleukin-10-secreting recombinant. Infect Immun. 1997 May;65(5):1931–1935. [PMC free article] [PubMed]
  • Menezes-de-Lima-Júnior O, Werneck-Barroso E, Cordeiro RS, Henriques MG. Effects of inhibitors of inflammatory mediators and cytokines on eosinophil and neutrophil accumulation induced by Mycobacterium bovis bacillus Calmette-Guérin in mouse pleurisy. J Leukoc Biol. 1997 Dec;62(6):778–785. [PubMed]
  • Moncada S, Palmer RM, Higgs EA. Nitric oxide: physiology, pathophysiology, and pharmacology. Pharmacol Rev. 1991 Jun;43(2):109–142. [PubMed]
  • Morrow PE. Dust overloading of the lungs: update and appraisal. Toxicol Appl Pharmacol. 1992 Mar;113(1):1–12. [PubMed]
  • Moura AC, Werneck-Barroso E, Rosas EC, Henriques MG, Cordeiro RS. Opposite cellular accumulation and nitric oxide production in vivo after pleural immunization with M. leprae or M. bovis BCG. Int J Mol Med. 1999 Jan;3(1):69–74. [PubMed]
  • Palmero DJ, Teres RI, Eiguchi K. Pulmonary disease due to Mycobacterium terrae. Tubercle. 1989 Dec;70(4):301–303. [PubMed]
  • Peters EJ, Morice R. Miliary pulmonary infection caused by Mycobacterium terrae in an autologous bone marrow transplant patient. Chest. 1991 Nov;100(5):1449–1450. [PubMed]
  • Pirhonen I, Nevalainen A, Husman T, Pekkanen J. Home dampness, moulds and their influence on respiratory infections and symptoms in adults in Finland. Eur Respir J. 1996 Dec;9(12):2618–2622. [PubMed]
  • Platt SD, Martin CJ, Hunt SM, Lewis CW. Damp housing, mould growth, and symptomatic health state. BMJ. 1989 Jun 24;298(6689):1673–1678. [PMC free article] [PubMed]
  • Rautiala S, Reponen T, Hyvärinen A, Nevalainen A, Husman T, Vehviläinen A, Kalliokoski P. Exposure to airborne microbes during the repair of moldy buildings. Am Ind Hyg Assoc J. 1996 Mar;57(3):279–284. [PubMed]
  • Seiler P, Aichele P, Raupach B, Odermatt B, Steinhoff U, Kaufmann SH. Rapid neutrophil response controls fast-replicating intracellular bacteria but not slow-replicating Mycobacterium tuberculosis. J Infect Dis. 2000 Feb;181(2):671–680. [PubMed]
  • Shimizu T, Furumoto H, Takahashi T, Yasuno H, Muto M. Lymphadenitis due to Mycobacterium terrae in an immunocompetent patient. Dermatology. 1999;198(1):97–98. [PubMed]
  • Spence TH, Ferris VM. Spontaneous resolution of a lung mass due to infection with Mycobacterium terrae. South Med J. 1996 Apr;89(4):414–416. [PubMed]
  • Strachan DP. Damp housing and childhood asthma: validation of reporting of symptoms. BMJ. 1988 Nov 12;297(6658):1223–1226. [PMC free article] [PubMed]
  • Taskinen T, Meklin T, Nousiainen M, Husman T, Nevalainen A, Korppi M. Moisture and mould problems in schools and respiratory manifestations in schoolchildren: clinical and skin test findings. Acta Paediatr. 1997 Nov;86(11):1181–1187. [PubMed]
  • Torkko P, Suutari M, Suomalainen S, Paulin L, Larsson L, Katila ML. Separation among species of Mycobacterium terrae complex by lipid analyses: comparison with biochemical tests and 16S rRNA sequencing. J Clin Microbiol. 1998 Feb;36(2):499–505. [PMC free article] [PubMed]
  • VanHeyningen TK, Collins HL, Russell DG. IL-6 produced by macrophages infected with Mycobacterium species suppresses T cell responses. J Immunol. 1997 Jan 1;158(1):330–337. [PubMed]
  • Van Snick J. Interleukin-6: an overview. Annu Rev Immunol. 1990;8:253–278. [PubMed]
  • Waegemaekers M, Van Wageningen N, Brunekreef B, Boleij JS. Respiratory symptoms in damp homes. A pilot study. Allergy. 1989 Apr;44(3):192–198. [PubMed]

Articles from Environmental Health Perspectives are provided here courtesy of National Institute of Environmental Health Science

Formats:

Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...

Links

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...