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Infection and Immunity, August 2008, p. 3511-3524, Vol. 76, No. 8
0019-9567/08/$08.00+0     doi:10.1128/IAI.00192-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Hookworm-Induced Persistent Changes to the Immunological Environment of the Lung{triangledown} ,{dagger}

Joshua J. Reece,1 Mark C. Siracusa,1 Teresa L. Southard,2 Cory F. Brayton,2 Joseph F. Urban Jr.,3 and Alan L. Scott1*

The W. Harry Feinstone Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland 21205,1 Department of Molecular and Comparative Pathobiology, School of Medicine, Johns Hopkins University, Baltimore, Maryland 21205,2 Beltsville Human Nutrition Research Center, Agricultural Research Service, U.S. Department of Agriculture, Beltsville, Maryland 207053

Received 12 February 2008/ Returned for modification 18 March 2008/ Accepted 15 May 2008

A number of important helminth parasites of humans have incorporated short-term residence in the lungs as an obligate phase of their life cycles. The significance of this transient pulmonary exposure to the infection and immunity is not clear. Employing a rodent model of infection with hookworm (Nippostrongylus brasiliensis), we characterized the long-term changes in the immunological status of the lungs induced by parasite infection. At 36 days after infection, alterations included a sustained increase in the transcription of both Th2 and Th1 cytokines as well as a significant increase in the number and frequency of alveolar macrophages displaying an alternatively activated phenotype. While N. brasiliensis did not induce alternate activation of lung macrophages in STAT6–/– animals, the parasite did induce a robust Th17 response in the pulmonary environment, suggesting that STAT6 signaling plays a role in modulating Th17 immunity and pathology in the lungs. In the context of the cellular and molecular changes induced by N. brasiliensis infection, there was a significant reduction in overall airway responsiveness and lung inflammation in response to allergen. In addition, the N. brasiliensis-altered pulmonary environment showed dramatic alterations in the nature and number of genes that were up- and downregulated in the lung in response to allergen challenge. The results demonstrate that even a transient exposure to a helminth parasite can effect significant and protracted changes in the immunological environment of the lung and that these complex molecular and cellular changes are likely to play a role in modulating a subsequent allergen-induced inflammatory response.

* Corresponding author. Mailing address: Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University, 615 North Wolfe Street, Baltimore, MD 21205. Phone: (410) 955-3430. Fax: (410) 955-0105. E-mail: ascott{at}jhsph.edu

{triangledown} Published ahead of print on 27 May 2008.

{dagger} Supplemental material for this article may be found at http://iai.asm.org/.

Editor: W. A. Petri, Jr.

Infection and Immunity, August 2008, p. 3511-3524, Vol. 76, No. 8
0019-9567/08/$08.00+0     doi:10.1128/IAI.00192-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Siracusa, M. C., Reece, J. J., Urban, J. F. Jr., Scott, A. L. (2008). Dynamics of lung macrophage activation in response to helminth infection. J. Leukoc. Biol. 84: 1422-1433 [Abstract] [Full Text]  


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