Appropriate dilutions were plated on BG blood agar plates with streptomycin and counted after 4 days of incubation at 37C to determine colony-forming units (CFU) per respiratory tract. analysis revealed that this IL-17-producing cells were macrophages and neutrophils as well as T cells, and were present predominantly in the airways rather than the lung tissue. Antibody neutralization of IL-17 significantly reduced chemokine gene expression and neutrophil recruitment to the airways, but only modestly increased peak bacterial loads. These data indicate that PT stimulates inflammatory responses by induction of Th1- and Th17-associated cytokines, including IL-17, during contamination in mice, but a role for IL-17 in protection against the infection remains to be established. Introduction is usually a Gram-negative bacterial pathogen that infects the human respiratory tract and causes an acute disease known as pertussis or whooping cough. The bacteria adhere to ciliated cells and proliferate within the upper and lower respiratory tract, and do not disseminate to other tissues [1]. A mouse model of respiratory tract contamination by this pathogen has been widely used to study the roles of various virulence factors, the associated pathology, and the immune responses elicited by the contamination. Although symptomatic disease (cough) and transmission are not observed in the mouse model, several characteristics of the human disease are present, such as bacterial multiplication and clearance, limitation of the contamination to the respiratory tract, and increased severity of contamination in infant mice [2], [3]. In addition, systemic effects of the disease observed in humans, such as leukocytosis and hypoglycemia, can be detected in infected mice [3]. These characteristics, as well as the availability of inbred mice and genetically altered immunodeficient Isobutyryl-L-carnitine strains, make the mouse model useful for the study of host immune responses to contamination. produces several virulence-associated factors that contribute to the ability of this pathogen to infect the respiratory tract and cause disease. Among these virulence factors are two secreted toxins, pertussis toxin (PT) and adenylate cyclase toxin (ACT), both of which have suppressive and modulatory effects around the immune response [1]. PT, which is usually produced exclusively by strains in the mouse model, our group has recently shown that PT contributes significantly to bacterial growth in the respiratory tract by effects on host cells of the airways, including inhibitory effects around the protective role of resident airway macrophages [4], [5], [6]. PT also inhibits early neutrophil influx to the airways after contamination by suppressing the early production of the neutrophil-attracting chemokines KC, LIX and MIP-2 by airway macrophages and epithelial cells [7].However, this latter property may not contribute significantly to bacterial growth, at least in na?ve mice, since neutrophil depletion did not increase bacterial loads, possibly because of the inhibitory activities of PT and ACT on neutrophils [8]. Several studies have shown that PT and ACT also modulate cytokine responses produced by immune cells and during contamination in the mouse model. ACT can upregulate major histocompatibility complex class II and costimulatory molecules on dendritic cells, inducing a semi-mature state that induces IL-10 production and decreases proinflammatory cytokine production [9], [10], [11]. However, ACT may also have proinflammatory properties since it can induce cyclooxygenase-2 (COX-2) and interleukin 6 hN-CoR (IL-6) production by macrophages in vitro [12]. PT can inhibit production of tumor necrosis factor-alpha (TNF-) and IL-6, as well as various chemokines, by mouse macrophages in response to LPS Isobutyryl-L-carnitine [8], [13], [14]. However, PT can also synergize with LPS to induce proinflammatory cytokine production by dendritic cells [15]. Therefore the modulatory activities of these toxins on cytokine production are complex and may depend on several variables, including host cell type and other bacterial factors. How these toxins modulate cytokine immune responses during contamination by is even less clear. Several recent studies on immunomodulation by have shown that the host immune response may be skewed towards expansion of a subset of T lymphocytes termed Th17 cells, which produce the cytokine IL-17A (hereafter referred to as IL-17) [16], despite earlier studies having indicated that contamination promotes a Th1 immune response (based largely on IFN- production) [2], Isobutyryl-L-carnitine [17]. Incubation of human dendritic cells with induced ACT-dependent manifestation of IL-23, a.