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The CRC 670 - Cell-autonomous Immunity
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The CRC 670 - Cell-autonomous Immunity

Brief desription

Immunity against microbial pathogens primarily depends on the recognition of pathogen components by innate receptors expressed on immune and non-immune cells. Innate receptors are evolutionarily conserved germ-line-encoded proteins and include TLRs (Toll-like receptors), NLRs (Nod-like receptors), and RLRs (RIG-I (retinoic acid-inducible gene-I)-like receptors).

The activation of these receptors results in induction of cell-autonomous antimicrobial effector mechanisms and in expression of cytokines, chemokines and co-stimulatory molecules, which also contribute to the elimination of pathogens and instruction of pathogen-specific adaptive immune responses.

In plants and animals, the NLR family of receptors perceives non-self and modified-self molecules inside host cells and mediates innate immune responses to microbial pathogens. An inflammatory response often requires additional stimuli elicited by endogenous molecules termed “damage-associated molecular patterns” (DAMPs). DAMPs are released by necrotic cells and include HMGB1, IL-1α, uric acid, DNA fragments, mitochondrial content, and ATP.

Despite similar biological functions and molecular architecture, animal NLRs are, in general, activated by conserved microbe- or damage-associated molecular patterns, whereas plant NLRs typically detect strain-specific pathogen effectors. Plant NLRs recognize either the effector structure or effector-mediated modifications of host proteins.

In the third funding period the CRC 670 continues to investigate into central areas of innate immunity:
i) molecular mechanisms underlying the co-operation of NLRs, RLRs, TLRs, and DAMPs in plant and animal cells;
ii) ligand specificities of cytosolic DNA and RNA receptors and emanating signal transduction pathways;
iii) physiologic significance of various forms of cell death with respect to release of DAMPs, inflammasomes and signalosomes; and
iv) cell type- and pathogen-specific activation requirements for autophagy and phagocytosis.

In particular, the concept of shared recognition and response mechanisms in plant and animal cell immunity will be revisited with combined bioinformatic and experimental forces. The availability of new reporter systems combined with intra-vital microscopy allows the in vivo investigation of the ´horizontal´ concept of cell-autonomous immunity, that is pericrine activity of inflammasomes, and/or other innate immune signalosomes on neighboring cells.

Innate immune responses triggered by the DNA damage response of infected host cells are an emerging topic of the CRC670. The identification and characterization of switch molecules that relay DNA damage response to cell-autonomous immune pathways will lead to new insights into functional links between cellular integrity and immunity.