Tohoku J. Exp. Med., 2007, 211(1)

Strain-Specific Pulmonary Defense Achieved after Repeated Airway Immunizations with Non-Typeable Haemophilus Influenzae in a Mouse Model

JUN KOYAMA,¹ KAMRUDDIN AHMED,² JIZI ZHAO,³ MARIKO SAITO,¹ SHOZABURO ONIZUKA,¹ KEITA OMA,¹ KIWAO WATANABE,¹ HIROSHI WATANABE¹ and KAZUNORI OISHI^1,3

¹Department of Internal Medicine, Institute of Tropical Medicine, Nagasaki University, Nagasaki, Japan
²Division of Infectious Diseases, Department of Social and Environmental Medicine, Institute of Scientific Research, Oita University, Oita, Japan
³Department of Special Pathogen, International Research Center for Infectious Diseases, Research Institute for Microbial Diseases, Osaka University, Suita, Japan

Strain-specific immune responses may play a critical role in the acute exacerbation of chronic obstructive pulmonary disease (COPD) caused by Haemophilus influenzae (NTHi), and the outer membrane protein P2 is one of surface antigens of NTHi, which may contribute to the strain-specific protective immunity. We examined whether repeated airway immunizations with killed-NTHi strains bearing different P2 molecules were capable of inducing protective immunity against homologous or heterologous strains in the lungs of a mouse model. Three different strains of NTHi were used in this study. Three serial intratracheal (IT) immuizations of a single strain or three different strains of NTHi led to the production of cross-reactive immunoglobulins G and A in bronchoalveolar lavage fluids. Three serial IT immunizations with a single strain enhanced the bacterial clearance of the homologous strain in the lungs, but no enhancement of bacterial clearance was found with three serial IT immunizations of heterologous strains. The enhancement in bacterial clearance, therefore, appears to be primarily strain-specific. Enhanced bacterial clearance of a hetrologous strain was also found after three serial IT immunizations of a single strain among two of the three strains employed for bacterial challenge. These findings suggest that P2 molecules and surface antigens other than P2 are involved in the development of pulmonary defense against NTHi in mice. Our data may explain, in part, why patients with COPD experience recurrent NTHi infections.

keywords —— non-typeable Haemophilus influenzae; outer membrane protein P2; pulmonary defense; chronic obstructive pulmonary disease; acute exacerbation

© 2007 Tohoku University Medical Press

===============================

Tohoku J. Exp. Med., 2007, 211, 63-74

Correspondence: Kazunori Oishi, Department of Special Pathogen, International Research Center for Infectious Diseases, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka 565-0871, Japan.

e-mail: oishik@biken.osaka-u.ac.jp