ATP released from macrophages with anthrax infection
MedWire News: Macrophages respond to the anthrax toxin by communicating with other immune cells using adenosine triphosphate (ATP), research shows.
ATP triggers the release of interleukin-1β (IL-1 β), and this alerts other macrophages in order to increase resistance to anthrax-induced cell death, report Michael Karin (University of California, San Diego) and colleagues in the journal Immunity.
"The warning alarm sounded during anthrax infection is elegant, complex and can be effective in slowing spread of the pathogen," said Karin.
Researchers had not been entirely sure how immune cells discriminate between virulent and nonvirulent bacteria.
One signaling system, the NOD-like receptor (NLR)-activated inflammasome system, does appear capable of discriminating between virulent and nonvirulent bacteria, they note.
In the present study, the group investigated the immune response caused by the toxin-producing strain of the Gram-positive pathogen Bacillus anthracis.
When infected with virulent B. anthracis, ATP is released from macrophages infected with the toxin. "Our results strongly suggest that the major source of ATP release from B. anthracis-infected macrophages is the connexin-43 ATP-release channel," note Karin and colleagues.
Although the virulent B. anthracis induced dephosphorylation and the opening of the connexin-43 ATP-release channel, a nonvirulent anthrax toxin did not, report investigators.
Next, the researchers showed that when ATP is released, the NLR-activated inflammasome system induces the secretion of IL-1 β.
IL-1 β secretion was shown essential for host protection against B. anthracis, resulting in the attenuation of macrophage death and bacterial clearance.
An analysis of the molecular events involved in B. anthracis-mediated inflammasome activation suggests that the key difference between virulent and nonvirulent strains of anthrax is their ability to induce ATP release from macrophages, say researchers.
Likewise, studies in mice showed that when the ATP channel is disrupted, or when the ATP receptor, inflammasome proteins, or the IL-1 β molecule are interfered with, the macrophages died.
"We hope these findings can be exploited for the design of new treatments to help the body combat serious bacterial pathogens," said Victor Nizet (University of California, San Diego), one of the study authors.
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