Mannose-binding lectin enhances Toll-like receptors 2 and 6 signaling from the phagosome.
Innate immunity is the first-line defense against pathogens and relies on phagocytes, soluble components, and cell-surface and cytosolic pattern recognition receptors. Despite using hard-wired receptors and signaling pathways, the innate immune response demonstrates surprising specificity to different pathogens. We determined how combinatorial use of innate immune defense mechanisms defines the response. We describe a novel cooperation between a soluble component of the innate immune system, the mannose-binding lectin, and Toll-like receptor 2 that both specifies and amplifies the host response to Staphylococcus aureus. Furthermore, we demonstrate that this cooperation occurs within the phagosome, emphasizing the importance of engulfment in providing the appropriate cellular environment to facilitate the synergy between these defense pathways.
Ip
W K Eddie
WK
Laboratory of Developmental Immunology, Department of Pediatrics, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA. eddie_ip@hms.harvard.edu
Takahashi
Kazue
K
Moore
Kathryn J
KJ
Stuart
Lynda M
LM
Ezekowitz
R Alan B
RA
D000818:Animals; D002460:Cell Line; D003167:Complement Activation; D019143:Evolution, Molecular; D006801:Humans; D007107:Immune System; D007113:Immunity, Innate; D037601:Mannose-Binding Lectin / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008954:Models, Biological; D010588:Phagosomes / Q000378:metabolism*; D040081:Protein Array Analysis; D013211:Staphylococcus aureus / Q000378:metabolism*; D051195:Toll-Like Receptor 2 / Q000378:metabolism*; D051216:Toll-Like Receptor 6 / Q000378:metabolism*
D037601:Mannose-Binding Lectin; C493486:Tlr2 protein, mouse; C495369:Tlr6 protein, mouse; D051195:Toll-Like Receptor 2; D051216:Toll-Like Receptor 6