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2012 ; 35
(6
): 437-49
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Alarmins, inflammasomes and immunity
#MMPMID23442356
Saïd-Sadier N
; Ojcius DM
Biomed J
2012[Nov]; 35
(6
): 437-49
PMID23442356
show ga
The elaboration of an effective immune response against pathogenic microbes such
as viruses, intracellular bacteria or protozoan parasites relies on the
recognition of microbial products called pathogen-associated molecular patterns
(PAMPs) by pattern recognition receptors (PRRs) such as Toll-like receptors
(TLRs). Ligation of the PRRs leads to synthesis and secretion of pro-inflammatory
cytokines and chemokines. Infected cells and other stressed cells also release
host-cell derived molecules, called damage-associated molecular patterns (DAMPs,
danger signals, or alarmins), which are generic markers for damage. DAMPs are
recognized by specific receptors on both immune and nonimmune cells, which,
depending on the target cell and the cellular context, can lead to cell
differentiation or cell death, and either inflammation or inhibition of
inflammation. Recent research has revealed that DAMPs and PAMPs synergize to
permit secretion of pro-inflammatory cytokines such as interleukin-1? (IL-1?):
PAMPs stimulate synthesis of pro-IL-1?, but not its secretion; while DAMPs can
stimulate assembly of an inflammasome containing, usually, a Nod-like receptor
(NLR) member, and activation of the protease caspase-1, which cleaves pro-IL-1?
into IL-1?, allowing its secretion. Other NLR members do not participate in
formation of inflammasomes but play other essential roles in regulation of the
innate immune response.
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