Previous Article | Next Article 
Infection and Immunity, October 1999, p. 5142-5150, Vol. 67, No. 10
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
Dual Role of Interleukin-10 in Murine Lyme Disease:
Regulation of Arthritis Severity and Host Defense
Jeanette P.
Brown,1
James F.
Zachary,2
Cory
Teuscher,2
Janis J.
Weis,1 and
R. Mark
Wooten1,*
Division of Cell Biology and Immunology,
Department of Pathology, University of Utah School of Medicine,
Salt Lake City, Utah 84132,1 and
Department of Veterinary Pathobiology, University of Illinois
at Urbana-Champaign, Urbana, Illinois 618022
Received 6 May 1999/Returned for modification 30 June 1999/Accepted 13 July 1999
In the murine model of Lyme disease, C3H/He mice exhibit severe
arthritis while C57BL/6N mice exhibit mild lesions when infected with
Borrelia burgdorferi. Joint tissues from these two strains of mice harbor similar concentrations of B. burgdorferi,
suggesting that the difference in disease severity reflects differences
in the magnitude of the inflammatory response to B. burgdorferi lipoproteins. Stimulation of bone marrow macrophages
from C3H/HeN mice with the B. burgdorferi lipoprotein OspA
resulted in higher-level production of the inflammatory mediators tumor
necrosis factor alpha, nitric oxide, and interleukin-6 (IL-6) than that
of macrophages from C57BL/6N mice. In contrast, macrophages from
C57BL/6N mice consistently produced larger amounts of the
anti-inflammatory cytokine IL-10 than did C3H/HeN macrophages. Addition
of recombinant IL-10 suppressed the production of inflammatory
mediators by macrophages from both strains. IL-10 was found to modulate
B. burgdorferi-induced inflammation in vivo, since C57BL/6J
mice deficient in IL-10 (IL-10
/
) developed more severe
arthritis than wild-type C57BL/6J mice. The increase in arthritis
severity was associated with a 10-fold decrease in the number of
B. burgdorferi organisms present in ankle tissues from
IL-10
/
mice. These findings suggest that in C57BL/6
mice, IL-10-dependent regulation of arthritis severity occurs at the
expense of effective control of bacterial numbers.
*
Corresponding author. Mailing address: Division of Cell
Biology and Immunology, Department of Pathology, University of Utah School of Medicine, 50 N. Medical Dr., Salt Lake City, UT 84132. Phone:
(801) 581-4364. Fax: (801) 581-4517. E-mail:
Mark.Wooten{at}path.med.utah.edu.
Infection and Immunity, October 1999, p. 5142-5150, Vol. 67, No. 10
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
This article has been cited by other articles:
-
McKinstry, K. K., Strutt, T. M., Buck, A., Curtis, J. D., Dibble, J. P., Huston, G., Tighe, M., Hamada, H., Sell, S., Dutton, R. W., Swain, S. L.
(2009). IL-10 Deficiency Unleashes an Influenza-Specific Th17 Response and Enhances Survival against High-Dose Challenge. J. Immunol.
182: 7353-7363
[Abstract]
[Full Text]
-
Raberg, L., Graham, A. L, Read, A. F
(2009). Decomposing health: tolerance and resistance to parasites in animals. Phil Trans R Soc B
364: 37-49
[Abstract]
[Full Text]
-
Tupin, E., Benhnia, M. R.-E.-I., Kinjo, Y., Patsey, R., Lena, C. J., Haller, M. C., Caimano, M. J., Imamura, M., Wong, C.-H., Crotty, S., Radolf, J. D., Sellati, T. J., Kronenberg, M.
(2008). NKT cells prevent chronic joint inflammation after infection with Borrelia burgdorferi. Proc. Natl. Acad. Sci. USA
105: 19863-19868
[Abstract]
[Full Text]
-
Londono, D., Marques, A., Hornung, R. L., Cadavid, D.
(2008). Relapsing Fever Borreliosis in Interleukin-10-Deficient Mice. Infect. Immun.
76: 5508-5513
[Abstract]
[Full Text]
-
Brown, C. R., Lai, A. Y.-C., Callen, S. T., Blaho, V. A., Hughes, J. M., Mitchell, W. J.
(2008). Adenoviral Delivery of Interleukin-10 Fails To Attenuate Experimental Lyme Disease. Infect. Immun.
76: 5500-5507
[Abstract]
[Full Text]
-
Londono, D., Marques, A., Hornung, R. L., Cadavid, D.
(2008). IL-10 Helps Control Pathogen Load during High-Level Bacteremia. J. Immunol.
181: 2076-2083
[Abstract]
[Full Text]
-
Wang, G., Petzke, M. M., Iyer, R., Wu, H., Schwartz, I.
(2008). Pattern of Proinflammatory Cytokine Induction in RAW264.7 Mouse Macrophages Is Identical for Virulent and Attenuated Borrelia burgdorferi. J. Immunol.
180: 8306-8315
[Abstract]
[Full Text]
-
Lazarus, J. J., Kay, M. A., McCarter, A. L., Wooten, R. M.
(2008). Viable Borrelia burgdorferi Enhances Interleukin-10 Production and Suppresses Activation of Murine Macrophages. Infect. Immun.
76: 1153-1162
[Abstract]
[Full Text]
-
Cruz, A. R., Moore, M. W., La Vake, C. J., Eggers, C. H., Salazar, J. C., Radolf, J. D.
(2008). Phagocytosis of Borrelia burgdorferi, the Lyme Disease Spirochete, Potentiates Innate Immune Activation and Induces Apoptosis in Human Monocytes. Infect. Immun.
76: 56-70
[Abstract]
[Full Text]
-
Iliopoulou, B. P., Alroy, J., Huber, B. T.
(2007). CD28 Deficiency Exacerbates Joint Inflammation upon Borrelia burgdorferi Infection, Resulting in the Development of Chronic Lyme Arthritis. J. Immunol.
179: 8076-8082
[Abstract]
[Full Text]
-
Woodman, M. E., Cooley, A. E., Miller, J. C., Lazarus, J. J., Tucker, K., Bykowski, T., Botto, M., Hellwage, J., Wooten, R. M., Stevenson, B.
(2007). Borrelia burgdorferi Binding of Host Complement Regulator Factor H Is Not Required for Efficient Mammalian Infection. Infect. Immun.
75: 3131-3139
[Abstract]
[Full Text]
-
Peterson, S. H., Nardelli, D. T., Warner, T. F., Callister, S. M., Torrealba, J. R., Schell, R. F.
(2007). Anti-p19 Antibody Treatment Exacerbates Lyme Arthritis and Enhances Borreliacidal Activity. CVI
14: 510-517
[Abstract]
[Full Text]
-
Gelderblom, H., Schmidt, J., Londono, D., Bai, Y., Quandt, J., Hornung, R., Marques, A., Martin, R., Cadavid, D.
(2007). Role of Interleukin 10 during Persistent Infection with the Relapsing Fever Spirochete Borrelia turicatae. Am. J. Pathol.
170: 251-262
[Abstract]
[Full Text]
-
Bolz, D. D., Sundsbak, R. S., Ma, Y., Akira, S., Weis, J. H., Schwan, T. G., Weis, J. J.
(2006). Dual Role of MyD88 in Rapid Clearance of Relapsing Fever Borrelia spp.. Infect. Immun.
74: 6750-6760
[Abstract]
[Full Text]
-
Crandall, H., Dunn, D. M., Ma, Y., Wooten, R. M., Zachary, J. F., Weis, J. H., Weiss, R. B., Weis, J. J.
(2006). Gene Expression Profiling Reveals Unique Pathways Associated with Differential Severity of Lyme Arthritis. J. Immunol.
177: 7930-7942
[Abstract]
[Full Text]
-
Lazarus, J. J., Meadows, M. J., Lintner, R. E., Wooten, R. M.
(2006). IL-10 Deficiency Promotes Increased Borrelia burgdorferi Clearance Predominantly through Enhanced Innate Immune Responses. J. Immunol.
177: 7076-7085
[Abstract]
[Full Text]
-
Dennis, V. A., Jefferson, A., Singh, S. R., Ganapamo, F., Philipp, M. T.
(2006). Interleukin-10 Anti-Inflammatory Response to Borrelia burgdorferi, the Agent of Lyme Disease: a Possible Role for Suppressors of Cytokine Signaling 1 and 3.. Infect. Immun.
74: 5780-5789
[Abstract]
[Full Text]
-
Behera, A. K., Hildebrand, E., Bronson, R. T., Perides, G., Uematsu, S., Akira, S., Hu, L. T.
(2006). MyD88 Deficiency Results in Tissue-Specific Changes in Cytokine Induction and Inflammation in Interleukin-18-Independent Mice Infected with Borrelia burgdorferi. Infect. Immun.
74: 1462-1470
[Abstract]
[Full Text]
-
Abel, B., Freigang, S., Bachmann, M. F., Boschert, U., Kopf, M.
(2005). Osteopontin Is Not Required for the Development of Th1 Responses and Viral Immunity. J. Immunol.
175: 6006-6013
[Abstract]
[Full Text]
-
Crandall, H., Ma, Y., Dunn, D. M., Sundsbak, R. S., Zachary, J. F., Olofsson, P., Holmdahl, R., Weis, J. H., Weiss, R. B., Teuscher, C., Weis, J. J.
(2005). Bb2Bb3 Regulation of Murine Lyme Arthritis Is Distinct from Ncf1 and Independent of the Phagocyte Nicotinamide Adenine Dinucleotide Phosphate Oxidase. Am. J. Pathol.
167: 775-785
[Abstract]
[Full Text]
-
Salazar, J. C., Pope, C. D., Moore, M. W., Pope, J., Kiely, T. G., Radolf, J. D.
(2005). Lipoprotein-Dependent and -Independent Immune Responses to Spirochetal Infection. CVI
12: 949-958
[Abstract]
[Full Text]
-
Benhnia, M. R.-E.-I., Wroblewski, D., Akhtar, M. N., Patel, R. A., Lavezzi, W., Gangloff, S. C., Goyert, S. M., Caimano, M. J., Radolf, J. D., Sellati, T. J.
(2005). Signaling through CD14 Attenuates the Inflammatory Response to Borrelia burgdorferi, the Agent of Lyme Disease. J. Immunol.
174: 1539-1548
[Abstract]
[Full Text]
-
Brown, C. R., Blaho, V. A., Loiacono, C. M.
(2004). Treatment of Mice with the Neutrophil-Depleting Antibody RB6-8C5 Results in Early Development of Experimental Lyme Arthritis via the Recruitment of Gr-1- Polymorphonuclear Leukocyte-Like Cells. Infect. Immun.
72: 4956-4965
[Abstract]
[Full Text]
-
Bolz, D. D., Sundsbak, R. S., Ma, Y., Akira, S., Kirschning, C. J., Zachary, J. F., Weis, J. H., Weis, J. J.
(2004). MyD88 Plays a Unique Role in Host Defense but Not Arthritis Development in Lyme Disease. J. Immunol.
173: 2003-2010
[Abstract]
[Full Text]
-
Al-Rasheed, A., Scheerens, H., Rennick, D.M., Fletcher, H.M., Tatakis, D.N.
(2003). Accelerated Alveolar Bone Loss in Mice Lacking Interleukin-10. JDR
82: 632-635
[Abstract]
[Full Text]
-
Liu, Y.-W., Tseng, H.-P., Chen, L.-C., Chen, B.-K., Chang, W.-C.
(2003). Functional Cooperation of Simian Virus 40 Promoter Factor 1 and CCAAT/Enhancer-Binding Protein {beta} and {delta} in Lipopolysaccharide-Induced Gene Activation of IL-10 in Mouse Macrophages. J. Immunol.
171: 821-828
[Abstract]
[Full Text]
-
Brown, C. R., Blaho, V. A., Loiacono, C. M.
(2003). Susceptibility to Experimental Lyme Arthritis Correlates with KC and Monocyte Chemoattractant Protein-1 Production in Joints and Requires Neutrophil Recruitment Via CXCR2. J. Immunol.
171: 893-901
[Abstract]
[Full Text]
-
Jobe, D. A., Lovrich, S. D., Schell, R. F., Callister, S. M.
(2003). C-Terminal Region of Outer Surface Protein C Binds Borreliacidal Antibodies in Sera from Patients with Lyme Disease. CVI
10: 573-578
[Abstract]
[Full Text]
-
Yoder, A., Wang, X., Ma, Y., Philipp, M. T., Heilbrun, M., Weis, J. H., Kirschning, C. J., Wooten, R. M., Weis, J. J.
(2003). Tripalmitoyl-S-Glyceryl-Cysteine-Dependent OspA Vaccination of Toll-Like Receptor 2-Deficient Mice Results in Effective Protection from Borrelia burgdorferi Challenge. Infect. Immun.
71: 3894-3900
[Abstract]
[Full Text]
-
Ji, J.-D., Tassiulas, I., Park-Min, K.-H., Aydin, A., Mecklenbrauker, I., Tarakhovsky, A., Pricop, L., Salmon, J. E., Ivashkiv, L. B.
(2003). Inhibition of Interleukin 10 Signaling after Fc Receptor Ligation and during Rheumatoid Arthritis. JEM
197: 1573-1583
[Abstract]
[Full Text]
-
Cepok, S., Zhou, D., Vogel, F., Rosche, B., Grummel, V., Sommer, N., Hemmer, B.
(2003). The Immune Response at Onset and During Recovery From Borrelia burgdorferi Meningoradiculitis. Arch Neurol
60: 849-855
[Abstract]
[Full Text]
-
Cole, N., Krockenberger, M., Stapleton, F., Khan, S., Hume, E., Husband, A. J., Willcox, M.
(2003). Experimental Pseudomonas aeruginosa Keratitis in Interleukin-10 Gene Knockout Mice. Infect. Immun.
71: 1328-1336
[Abstract]
[Full Text]
-
Lisinski, T. J., Furie, M. B.
(2002). Interleukin-10 inhibits proinflammatory activation of endothelium in response to Borrelia burgdorferi or lipopolysaccharide but not interleukin-1{beta} or tumor necrosis factor {alpha}. J. Leukoc. Biol.
72: 503-511
[Abstract]
[Full Text]
-
Giambartolomei, G. H., Dennis, V. A., Lasater, B. L., Murthy, P. K., Philipp, M. T.
(2002). Autocrine and Exocrine Regulation of Interleukin-10 Production in THP-1 Cells Stimulated with Borrelia burgdorferi Lipoproteins. Infect. Immun.
70: 1881-1888
[Abstract]
[Full Text]
-
Potter, M. R., Rittling, S. R., Denhardt, D. T., Roper, R. J., Weis, J. H., Teuscher, C., Weis, J. J.
(2002). Role of Osteopontin in Murine Lyme Arthritis and Host Defense against Borrelia burgdorferi. Infect. Immun.
70: 1372-1381
[Abstract]
[Full Text]
-
Liang, F. T., Jacobs, M. B., Bowers, L. C., Philipp, M. T.
(2002). An Immune Evasion Mechanism for Spirochetal Persistence in Lyme Borreliosis. JEM
195: 415-422
[Abstract]
[Full Text]
-
Wooten, R. M., Ma, Y., Yoder, R. A., Brown, J. P., Weis, J. H., Zachary, J. F., Kirschning, C. J., Weis, J. J.
(2002). Toll-Like Receptor 2 Is Required for Innate, But Not Acquired, Host Defense to Borrelia burgdorferi. J. Immunol.
168: 348-355
[Abstract]
[Full Text]
-
Bockenstedt, L. K., Kang, I., Chang, C., Persing, D., Hayday, A., Barthold, S. W.
(2001). CD4+ T Helper 1 Cells Facilitate Regression of Murine Lyme Carditis. Infect. Immun.
69: 5264-5269
[Abstract]
[Full Text]
-
Wang, G., Ojaimi, C., Iyer, R., Saksenberg, V., McClain, S. A., Wormser, G. P., Schwartz, I.
(2001). Impact of Genotypic Variation of Borrelia burgdorferi Sensu Stricto on Kinetics of Dissemination and Severity of Disease in C3H/HeJ Mice. Infect. Immun.
69: 4303-4312
[Abstract]
[Full Text]
-
Glickstein, L., Edelstein, M., Dong, J. Z.
(2001). Gamma Interferon Is Not Required for Arthritis Resistance in the Murine Lyme Disease Model. Infect. Immun.
69: 3737-3743
[Abstract]
[Full Text]
-
Toth, L. A., Opp, M. R.
(2001). Cytokine- and microbially induced sleep responses of interleukin-10 deficient mice. Am. J. Physiol. Regul. Integr. Comp. Physiol.
280: R1806-R1814
[Abstract]
[Full Text]
-
Thomas, V., Anguita, J., Barthold, S. W., Fikrig, E.
(2001). Coinfection with Borrelia burgdorferi and the Agent of Human Granulocytic Ehrlichiosis Alters Murine Immune Responses, Pathogen Burden, and Severity of Lyme Arthritis. Infect. Immun.
69: 3359-3371
[Abstract]
[Full Text]
-
Gergel, E. I., Furie, M. B.
(2001). Activation of Endothelium by Borrelia burgdorferi In Vitro Enhances Transmigration of Specific Subsets of T Lymphocytes. Infect. Immun.
69: 2190-2197
[Abstract]
[Full Text]
-
Murthy, P. K., Dennis, V. A., Lasater, B. L., Philipp, M. T.
(2000). Interleukin-10 Modulates Proinflammatory Cytokines in the Human Monocytic Cell Line THP-1 Stimulated with Borrelia burgdorferi Lipoproteins. Infect. Immun.
68: 6663-6669
[Abstract]
[Full Text]
-
Ganapamo, F., Dennis, V. A., Philipp, M. T.
(2000). Early Induction of Gamma Interferon and Interleukin-10 Production in Draining Lymph Nodes from Mice Infected with Borrelia burgdorferi. Infect. Immun.
68: 7162-7165
[Abstract]
[Full Text]
-
Potter, M. R., Noben-Trauth, N., Weis, J. H., Teuscher, C., Weis, J. J.
(2000). Interleukin-4 (IL-4) and IL-13 Signaling Pathways Do Not Regulate Borrelia burgdorferi-Induced Arthritis in Mice: IgG1 Is Not Required for Host Control of Tissue Spirochetes. Infect. Immun.
68: 5603-5609
[Abstract]
[Full Text]
-
Brown, C. R., Reiner, S. L.
(2000). Bone-Marrow Chimeras Reveal Hemopoietic and Nonhemopoietic Control of Resistance to Experimental Lyme Arthritis. J. Immunol.
165: 1446-1452
[Abstract]
[Full Text]
-
Straubinger, R. K.
(2000). PCR-Based Quantification of Borrelia burgdorferi Organisms in Canine Tissues over a 500-Day Postinfection Period. J. Clin. Microbiol.
38: 2191-2199
[Abstract]
[Full Text]