Signaling pathway for phagocyte priming upon encounter with apoptotic cells.
The phagocytic elimination of cells undergoing apoptosis is an evolutionarily conserved innate immune mechanism for eliminating unnecessary cells. Previous studies showed an increase in the level of engulfment receptors in phagocytes after the phagocytosis of apoptotic cells, which leads to the enhancement of their phagocytic activity. However, precise mechanisms underlying this phenomenon require further clarification. We found that the pre-incubation of aDrosophilaphagocyte cell line with the fragments of apoptotic cells enhanced the subsequent phagocytosis of apoptotic cells, accompanied by an augmented expression of the engulfment receptors Draper and integrin αPS3. The DNA-binding activity of the transcription repressor Tailless was transiently raised in those phagocytes, depending on two partially overlapping signal-transduction pathways for the induction of phagocytosis as well as the occurrence of engulfment. The RNAi knockdown oftaillessin phagocytes abrogated the enhancement of both phagocytosis and engulfment receptor expression. Furthermore, the hemocyte-specific RNAi oftaillessreduced apoptotic cell clearance inDrosophilaembryos. Taken together, we propose the following mechanism for the activation ofDrosophilaphagocytes after an encounter with apoptotic cells: two partially overlapping signal-transduction pathways for phagocytosis are initiated; transcription repressor Tailless is activated; expression of engulfment receptors is stimulated; and phagocytic activity is enhanced. This phenomenon most likely ensures the phagocytic elimination of apoptotic cells by stimulated phagocytes and is thus considered as a mechanism to prime phagocytes in innate immunity.
From the Graduate School of Medical Sciences and.
Saori
0000-0003-2672-3082
S
Nonaka
From the Graduate School of Medical Sciences and.
Yuki
Y
Ando
From the Graduate School of Medical Sciences and.
Takuto
T
Kanetani
School of Pharmacy, Kanazawa University, Kanazawa, Ishikawa 920-1192, Japan.
Chiharu
C
Hoshi
the Institute for Food Sciences, Hirosaki University, Aomori, Aomori 038-0012, Japan, and.
Yuji
Y
Nakai
From the Graduate School of Medical Sciences and.|the Faculty of Pharmacy, Hasanuddin University, Makassar, South Sulawesi 90245, Indonesia.
Firzan
0000-0003-0989-4023
F
Nainu
the Institute for Food Sciences, Hirosaki University, Aomori, Aomori 038-0012, Japan, and.
Kaz
0000-0002-1695-2562
K
Nagaosa
From the Graduate School of Medical Sciences and.
Akiko
0000-0002-7811-4409
A
Shiratsuchi
From the Graduate School of Medical Sciences and nakanaka@p.kanazawa-u.ac.jp.|School of Pharmacy, Kanazawa University, Kanazawa, Ishikawa 920-1192, Japan.
Yoshinobu
0000-0002-8767-3587
Y
Nakanishi
D000818:Animals; D017209:Apoptosis; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D003513:Cycloheximide / Q000737:chemistry; D003598:Cytoskeletal Proteins / Q000378:metabolism; D004247:DNA / Q000032:analysis; D029721:Drosophila Proteins / Q000378:metabolism; D004331:Drosophila melanogaster / Q000378:metabolism; D006434:Hemocytes / Q000166:cytology; D007113:Immunity, Innate; D039001:Integrin alpha Chains / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D050736:Oncogene Protein v-crk / Q000378:metabolism; D010586:Phagocytes / Q000166:cytology*; D010587:Phagocytosis; D034622:RNA Interference; D012097:Repressor Proteins / Q000378:metabolism; D015398:Signal Transduction
D003598:Cytoskeletal Proteins; D029721:Drosophila Proteins; D039001:Integrin alpha Chains; D008565:Membrane Proteins; D050736:Oncogene Protein v-crk; D012097:Repressor Proteins; C074090:TLL protein, Drosophila; C572269:alpha PS3 integrin, Drosophila; C495322:drpr protein, Drosophila; C107441:mbc protein, Drosophila; D004247:DNA; D003513:Cycloheximide
Drosophila; apoptosis; gene regulation; phagocytosis; signal transduction; transcription repressor