Hookworm-induced persistent changes to the immunological environment of the lung.
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.
Reece
Joshua J
JJ
Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University, 615 North Wolfe Street, Baltimore, MD 21205, USA.
Siracusa
Mark C
MC
Southard
Teresa L
TL
Brayton
Cory F
CF
Urban
Joseph F
JF
Scott
Alan L
AL
D000485:Allergens / Q000276:immunology; D000818:Animals; D016207:Cytokines / Q000096:biosynthesis; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D008168:Lung / Q000276:immunology* / Q000469:parasitology*; D008262:Macrophage Activation; D016676:Macrophages, Alveolar / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D009559:Nippostrongylus / Q000276:immunology*; D020411:Oligonucleotide Array Sequence Analysis; D050800:STAT6 Transcription Factor / Q000172:deficiency
D000485:Allergens; D016207:Cytokines; D050800:STAT6 Transcription Factor; C494100:Stat6 protein, mouse