IL-17 Is a Critical Component of Vaccine-Induced Protection against Lung Infection by Lipopolysaccharide-Heterologous Strains of Pseudomonas aeruginosa

Abstract

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 PA14ΔaroA, was constructed. PA14ΔaroA-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 PA14ΔaroA-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, PA14ΔaroA-immunized mice had more rapid recruitment of neutrophils to the airways early after challenge. T cells isolated from P. aeruginosa ΔaroA-immunized mice proliferated and produced IL-17 in high quantities after coculture with gentamicin-killed P. aeruginosa. Six hours following challenge, PA14ΔaroA-immunized mice had significantly higher levels of IL-17 in bronchoalveolar lavage fluid compared with unimmunized, Escherichia coli-immunized, or PAO1ΔaroA-immunized mice. Antibody-mediated depletion of IL-17 before challenge or absence of the IL-17 receptor abrogated the PA14ΔaroA vaccine’s protection against lethal pneumonia. These data show that IL-17 plays a critical role in antibody-independent vaccine-induced protection against LPS-heterologous strains of P. aeruginosa in the lung.

IL-17 Is Necessary for Host Protection against Acute-Phase Trypanosoma cruzi Infection

“…IL-17A induced during infection of bacteria and fungi and a protozoan parasite Toxoplasma gondii mobilizes neutrophils for elimination of the pathogens (28,29,31,48). However, in the current study, deficiency in IL-17A did not affect the number of immunerelated cells migrating into infected tissues (Fig.…”

“…The roles of IL-17A in host defense against intracellular protozoan parasites remain to be fully elucidated, although IL-17A has a role in the host's protection against fungal and bacterial infection (28)(29)(30)(31). Therefore, we investigated the role of IL-17A in T. cruzi infection.…”

Attenuated Bordetella pertussis Vaccine Protects against Respiratory Syncytial Virus Disease via an IL-17–Dependent Mechanism

“…Furthermore, Th17 responses have been shown to be beneficial in other types of viral airway inflammation (28) and in the defense against pneumonia, where IL-17 is crucial for antibody-independent protection against Pseudomonas aeruginosa (44).…”

Synthesis, Characterization, and Immunological Properties of LPS-Based Vaccines Composed of O-Polysaccharides Conjugated with Recombinant Exoprotein A from <i>Pseudomonas aeruginosa</i>

“…LPS is an important immunoreactive surface antigen of P. aeruginosa [6] [9], and is composed of a hydrophilic O-polysaccharide (O-PS) region that is linked to a hydrophobic lipid A via a core oligosaccharide. Twenty major serotypes of P. aeruginosa have been identified on the basis of their antigenic O-PS cross reactivity and chemical structure 0 [10].…”