期刊
JOURNAL OF IMMUNOLOGY
卷 181, 期 7, 页码 4965-4975出版社
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.181.7.4965
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资金
- National Institutes of Health [K08 AI50036, R21 HL079423, R01AI068112, AI22535]
In a murine model of acute fatal pneumonia, we previously showed that nasal immunization with a live-attenuated aroA deletant of Pseudomonas aeruginosa strain PAO1 elicited LPS serogroup-specific protection, indicating that opsonic Ab to the LPS O Ag was the most important immune effector. Because P. aeruginosa strain PA14 possesses additional virulence factors, we hypothesized that a live-attenuated vaccine based on PA14 might elicit a broader array of immune effectors. Thus, an aroA deletant of PA14, denoted PA14 Delta aroA, was constructed. PA14 Delta aroA-immunized mice were protected against lethal pneumonia caused not only by the parental strain but also by cytotoxic variants of the O Ag-heterologous P. aeruginosa strains PAO1 and PAO6a,d. Remarkably, serum from PA14 Delta aroA-immunized mice had very low levels of opsonic activity against strain PAO1 and could not passively transfer protection, suggesting that an antibody-independent mechanism was needed for the observed cross-serogroup protection. Compared with control mice, PA14 Delta aroA-immunized mice had more rapid recruitment of neutrophils to the airways early after challenge. T cells isolated from A aeruginosa Delta aroA-immunized mice proliferated and produced IL-17 in high quantities after coculture with gentamicin-killed P. aeruginosa. Six hours following challenge, PA14 Delta aroA-immunized mice had significantly higher levels of IL-17 in bronchoalveolar lavage fluid compared with unimmunized, Escherichia coli-immunized, or PAO1 Delta aroA-immunized mice. Antibody-mediated depletion of IL-17 before challenge or absence of the IL-17 receptor abrogated the PA14 Delta aroA vaccine's protection against lethal pneumonia. These data show that 11,47 plays a critical role in antibody-independent vaccine-induced protection against LPS-heterologous strains of P. aeruginosa in the lung.
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