Adenylate cyclase toxin (CyaA) is released in the course of B. pertussis infection in the host's respiratory tract in order to suppress its early innate and subsequent adaptive immune defense. CD11b-expressing dendritic cells (DC), macrophages and neutrophils are professional phagocytes and key players of the innate immune system that provide a first line of defense against invading pathogens. Recent findings revealed the capacity of B. pertussis CyaA to intoxicate DC with high concentrations of 3',5'-cyclic adenosine monophosphate (cAMP), which ultimately skews the host immune response towards the expansion of Th17 cells and regulatory T cells. CyaA-induced cAMP signaling swiftly incapacitates opsonophagocytosis, oxidative burst and NO-mediated killing of bacteria by neutrophils and macrophages. The subversion of host immune responses by CyaA after delivery into DC, macrophages and neutrophils is the subject of this review.

Department of Immunology 2nd Faculty of Medicine Charles University and University Hospital Motol Prague 150 00 Czech Republic

Department of Infectious Diseases Istituto Superiore di Sanità Rome 00161 Italy

Faculty of Science Charles University Prague Prague 128 00 Czech Republic

Institute of Microbiology of the CAS v v i Prague 142 20 Czech Republic

Sotio a s Prague170 00 Czech Republic

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Pertussis toxin suppresses dendritic cell-mediated delivery of B. pertussis into lung-draining lymph nodes

Acyclic nucleoside phosphonates with 2-aminothiazole base as inhibitors of bacterial and mammalian adenylate cyclases

Almost half of the RTX domain is dispensable for complement receptor 3 binding and cell-invasive activity of the Bordetella adenylate cyclase toxin

Adenylate Cyclase Toxin Tinkering With Monocyte-Macrophage Differentiation

Bordetella Type III Secretion Injectosome and Effector Proteins