Both lethal and edema toxins of Bacillus anthracis disrupt the human dendritic cell chemokine network.

Bacillus anthracis, the agent of anthrax, produces two main virulence factors: a capsule and two toxins. Both lethal toxin (LT) and edema toxin (ET) paralyze the immune defense system. Here, we analyze the effects of LT and ET on the capacity of human monocyte-derived dendritic cells (MoDC) to produce proinflammatory chemokines.

Shape-based tracking allows functional discrimination of two immune cell subsets expressing the same fluorescent tag in mouse lung explant.

Dendritic Cells (DC) represent a key lung immune cell population, which play a critical role in the antigen presenting process and initiation of the adaptive immune response. The study of DCs has largely benefited from the joint development of fluorescence microscopy and knock-in technology, leading to several mouse strains with constitutively labeled DC subsets. However, in the lung most transgenic mice do express fluorescent protein not only in DCs, but also in closely related cell lineages such as monocytes and macrophages.

Differential role of the interleukin-17 axis and neutrophils in resolution of inhalational anthrax.

The roles of interleukin-17 (IL-17) and neutrophils in the lung have been described as those of two intricate but independent players. Here we identify neutrophils as the primary IL-17-secreting subset of cells in a model of inhalation anthrax using A/J and C57BL/6 mice. With IL-17 receptor A knockout (IL-17RA-/-) mice, we confirmed that IL-17A/F signaling is instrumental in the self-recruitment of this population.

Anthrax toxins: a weapon to systematically dismantle the host immune defenses.

Successful colonization of the host by bacterial pathogens relies on their capacity to evade the complex and powerful defenses opposed by the host immune system, at least in the initial phases of infection. The two toxins of Bacillus anthracis, lethal toxin and edema toxin, appear to have been shaped by evolution to assist the microorganism in this crucial function, in addition to act as general toxins acting on almost all cell types. Edema toxin causes a consistent elevation of cAMP, an important second messenger the production of which is normally strictly controlled in mammalian cells, whereas lethal toxin cleaves most isoforms of mitogen-activated protein kinase kinases.

Anthrax, toxins and vaccines: a 125-year journey targeting Bacillus anthracis.

Bacillus anthracis is the causative agent of anthrax, a disease that plagues both humans and various animal species. Effective vaccines are available, but those approved for human use are crude culture supernatants that require multiple injections and a yearly boost. Many experts agree that it is now time for the next generation of human vaccines against anthrax.

Lung dendritic cells rapidly mediate anthrax spore entry through the pulmonary route.

Inhalational anthrax is a life-threatening infectious disease of considerable concern, especially because anthrax is an emerging bioterrorism agent. The exact mechanisms leading to a severe clinical form through the inhalational route are still unclear, particularly how immobile spores are captured in the alveoli and transported to the lymph nodes in the early steps of infection. We investigated the roles of alveolar macrophages and lung dendritic cells (LDC) in spore migration.

Contribution of toxins to the pathogenesis of inhalational anthrax.

Inhalational anthrax is a life-threatening infectious disease of considerable concern, especially as a potential bioterrorism agent. Progress is gradually being made towards understanding the mechanisms used by Bacillus anthracis to escape the immune system and to induce severe septicaemia associated with toxaemia and leading to death. Recent advances in fundamental research have revealed previously unsuspected roles for toxins in various cell types.

[Anthrax revisited: Bacillus anthracis toxins as novel actors of immune escape?].

The recent bioterrorist attacks have stressed the need of a better knowledge of Bacillus anthracis infection pathophysiology. We present here the increasing interests of B. anthracis studies in term of bio-defense, the main pathogen characteristics, the main clinical features of inhalational anthrax (the pulmonary form of the disease), and recent aspects of its physiopathology.

Resident CD11c+ lung cells are impaired by anthrax toxins after spore infection.

Bacillus anthracis secretes 2 toxins: lethal toxin (LT) and edema toxin (ET). We investigated their role in the physiopathologic mechanisms of inhalational anthrax by evaluating murine lung dendritic cell (LDC) functions after infection with B. anthracis strains secreting LT, ET, or both or with a nontoxinogenic strain.

Evidence for adjuvanticity of anthrax edema toxin.

Bacillus anthracis edema factor (EF) is an adenylate cyclase that increases intracellular cAMP concentrations. Since EF is present as a contaminant in the licensed protective antigen(PA)-based vaccines, we investigated its effect on anti-PA humoral immune response in BALB/c mice. We observed a significant increase of anti-PA IgG response in mice immunised with PA in association with EF as compared to PA alone.

Anthrax edema toxin cooperates with lethal toxin to impair cytokine secretion during infection of dendritic cells.

Bacillus anthracis secretes two critical virulence factors, lethal toxin (LT) and edema toxin (ET). In this study, we show that murine bone marrow-derived dendritic cells (DC) infected with B. anthracis strains secreting ET exhibit a very different cytokine secretion pattern than DC infected with B.

Fever-like thermal conditions regulate the activation of maturing dendritic cells.

Fever is one of the most frequent clinical signs encountered in pathology, especially with respect to infectious diseases. It is currently thought that the role of fever on immunity is limited to activation of innate immunity; however, its relevance to activation of adaptive immunity remains unclear. Dendritic cells (DCs) that behave as sentinels of the immune system provide an important bridge between innate and adaptive immunity.