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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 ^,

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.

Published ahead of print on 27 May 2008.

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Editor: W. A. Petri, Jr.