Roles of Interleukin-17 in an Experimental Legionella pneumophila Pneumonia Model

Abstract

Interleukin-17 (IL-17) is a key factor in T helper type 17 (Th17) lineage host responses and plays critical roles in immunological control of a variety of infectious diseases. Although Legionella pneumophila, an intracellular bacterium found widely in the environment, often causes a serious and life-threatening pneumonia in humans, the contribution of IL-17 to immune function during Legionella pneumonia is unknown. In the present study, we used an experimental Legionella pneumonia infection to clarify the role of IL-17 in the resulting immune response. We observed robust production of pulmonary IL-17A and IL-17F (IL-17A/ F), peaking on day 1 and declining thereafter. Upregulated production of tumor necrosis factor alpha (TNF-␣), IL-6, and IL-1␤, but not monocyte chemotactic protein 1 (MCP-1), was observed in Legionella-infected bone marrow-derived macrophages from BALB/c mice that had been stimulated with IL-17A or IL-17F. A significant decrease in the production of proinflammatory cytokines IL-6 and TNF-␣ was observed in IL-17A/F-deficient mice (BALB/c background) infected with L. pneumophila. Moreover, we found impaired neutrophil migration and lower numbers of chemokines (KC, LIX, and MIP-2) in IL-17A/F-deficient mice. IL-17A/F-deficient mice also eliminated L. pneumophila more slowly and were less likely to survive a lethal challenge. These results demonstrate that IL-17A/F plays a critical role in L. pneumophila pneumonia, probably through induction of proinflammatory cytokines and accumulation of neutrophils at the infection site.

Comparison of innate immune agonists for induction of tracheal antimicrobial peptide gene expression in tracheal epithelial cells of cattle

“…IL-17 is important for defence of the respiratory tract against bacterial pathogens including Staphylococcus aureus, Pseudomonas aeruginosa and Legionella pneumophila infections in mice [30][31][32]. In the present study, IL-17A receptor subunit A gene expression was identified in bTEC, consistent with prior findings in human airway epithelial cells [33].…”

Biofilm-Infected Intracerebroventricular Shunts Elicit Inflammation within the Central Nervous System

“…It is possible that sustained CXCL2 levels allow for continued recruitment of new neutrophils in an attempt to resolve the infection, although other chemokines or alternative neutrophil chemoattractants such as complement split products and/or bacterium-derived N-formyl-methionyl peptides (f-MetLeu-Phe) not examined in the current study may also participate in this process. IL-17 is an important antimicrobial cytokine, known to play an important role in the response to brain abscesses and cutaneous infections caused by S. aureus as well as other models of infection (1,12,24,30,33). In the setting of a catheter-based infection, IL-17 expression is significantly higher in infected than in sterile …”

IFN-γ induction by neutrophil-derived IL-17A homodimer augments pulmonary antibacterial defense

“…In a recent investigation, Il17a/Il17f −/− mice on a Balb/c background were utilized to show that IL-17A/F is important for controlling bacterial burden, inducing neutrophil influx into the lung, and for survival in response to L. pneumophila 15 . However, to further expand upon this initial study, we used: 1) single and double knockout mice on C57Bl/6 background and antibody blocking in A/J mice; 2) the role of IL-17A or IL-17F individually or together are important for host defense; 3) bone marrow chimeras and adoptive transfer experiments to determine which cell types are responsible for IL-17A and IL-17F production; 4) IL-17 homodimer (IL-17A or IL-17F) or heterodimer (IL-17A/F) to determine which is more effective at inducing host resistance; and 5) IL-17-mediates IFN-γ production via paracrine manner to induce host defense.…”