Diversity of innate immune recognition mechanism for bacterial polymeric meso-diaminopimelic acid-type peptidoglycan in insects.
In Drosophila, the synthesis of antimicrobial peptides in response to microbial infections is under the control of the Toll and immune deficiency (Imd) signaling pathway. The Toll signaling pathway responds mainly to the lysine-type peptidoglycan of Gram-positive bacteria and fungal β-1,3-glucan, whereas the Imd pathway responds to the meso-diaminopimelic acid (DAP)-type peptidoglycan of Gram-negative bacteria and certain Gram-positive bacilli. Recently we determined the activation mechanism of a Toll signaling pathway biochemically using a large beetle, Tenebrio molitor. However, DAP-type peptidoglycan recognition mechanism and its signaling pathway are still unclear in the fly and beetle. Here, we show that polymeric DAP-type peptidoglycan, but not its monomeric form, formed a complex with Tenebrio peptidoglycan recognition protein-SA, and this complex activated the three-step proteolytic cascade to produce processed Spätzle, a Toll receptor ligand, and induced Drosophila defensin-like antimicrobial peptide in Tenebrio larvae similarly to polymeric lysine-type peptidoglycan. Monomeric DAP-type peptidoglycan induced Drosophila diptericin-like antimicrobial peptide in Tenebrio hemocytes. In addition, both polymeric and monomeric DAP-type peptidoglycans induced expression of Tenebrio peptidoglycan recognition protein-SC2, which is DAP-type peptidoglycan-selective N-acetylmuramyl-l-alanine amidase that functions as a DAP-type peptidoglycan scavenger, appearing to function as a negative regulator of the DAP-type peptidoglycan signaling by cleaving DAP-type peptidoglycan in Tenebrio larvae. Taken together, these results demonstrate that molecular recognition mechanism for polymeric DAP-type peptidoglycan is different between Tenebrio larvae and Drosophila adults, providing biochemical evidences of biological diversity of innate immune responses in insects.
Yu
Yang
Y
From the National Research Laboratory of Defense Proteins, College of Pharmacy, Pusan National University, Busan 609-735, Korea.
Park
Ji-Won
JW
From the National Research Laboratory of Defense Proteins, College of Pharmacy, Pusan National University, Busan 609-735, Korea.
Kwon
Hyun-Mi
HM
From the National Research Laboratory of Defense Proteins, College of Pharmacy, Pusan National University, Busan 609-735, Korea.
Hwang
Hyun-Ok
HO
From the National Research Laboratory of Defense Proteins, College of Pharmacy, Pusan National University, Busan 609-735, Korea.
Jang
In-Hwan
IH
Division of Molecular Life Science, Ewha Woman's University, Seoul 120-750, Korea.
Masuda
Akiko
A
Biomolecular Characterization Team, RIKEN, Wako 351-0198, Japan; Core Research for Evolutional Science and Technology, Japan Science and Technology Agency, Tokyo 102-0075, Japan.
Kurokawa
Kenji
K
From the National Research Laboratory of Defense Proteins, College of Pharmacy, Pusan National University, Busan 609-735, Korea.
Nakayama
Hiroshi
H
Biomolecular Characterization Team, RIKEN, Wako 351-0198, Japan; Core Research for Evolutional Science and Technology, Japan Science and Technology Agency, Tokyo 102-0075, Japan.
Lee
Won-Jae
WJ
Division of Molecular Life Science, Ewha Woman's University, Seoul 120-750, Korea.
Dohmae
Naoshi
N
Biomolecular Characterization Team, RIKEN, Wako 351-0198, Japan; Core Research for Evolutional Science and Technology, Japan Science and Technology Agency, Tokyo 102-0075, Japan.
Zhang
Jinghai
J
School of Life Science and Biopharmaceutics, Shenyang Pharmaceutical University, Shenyang 110016, China.
Lee
Bok Luel
BL
From the National Research Laboratory of Defense Proteins, College of Pharmacy, Pusan National University, Busan 609-735, Korea. Electronic address: brlee@pusan.ac.kr.
D000818:Animals; D001419:Bacteria / Q000276:immunology* / Q000378:metabolism; D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D023082:Defensins / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D003960:Diaminopimelic Acid; D029721:Drosophila Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D004331:Drosophila melanogaster; D007113:Immunity, Innate / Q000502:physiology; D019476:Insect Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D008969:Molecular Sequence Data; D010457:Peptidoglycan / Q000276:immunology* / Q000378:metabolism; D013045:Species Specificity; D013712:Tenebrio / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology
D002352:Carrier Proteins; D023082:Defensins; D029721:Drosophila Proteins; D019476:Insect Proteins; D010457:Peptidoglycan; C118897:peptidoglycan recognition protein; C086179:spz protein, Drosophila; D003960:Diaminopimelic Acid