Homeodomain proteins POU‐M2, antennapedia and abdominal‐B are involved in regulation of the segment‐specific expression of the clip‐domain serine protease gene <i>CLIP13</i> in the silkworm, <i>Bombyx mori</i>

Liu, Huawei; Heng, Jingya; Wang, Luoling; Li, Youshan; Tang, Xin; Huang, Xuan; Xia, Qingyou; Zhao, Ping

doi:10.1111/1744-7917.12916

Cited by 3 publications

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“…CLIP11 (BmSPH-1) plays a dual role in the melanization of the pupal cuticle and the immune response of hemocytes [38], whereas CLIP13 (BmSP95) is inducible by 20E and is involved in silkworm cuticle remodeling during molting and metamorphosis [39,40]. Moreover, B. mori CLIP1 (PPAE, BmSP133) is involved in the activation of proPO [41,42].…”

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confidence: 99%

Serpin-1a and serpin-6 regulate the Toll pathway immune homeostasis by synergistically inhibiting the Spätzle-processing enzyme CLIP2 in silkworm, Bombyx mori

Liu,

Xu,

Wang

et al. 2023

PLoS Pathog

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The Toll receptor signaling pathway is an important innate immune response of insects to pathogen infection; its extracellular signal transduction involves serine protease cascade activation. However, excessive or constitutive activation of the Toll pathway can be detrimental. Hence, the balance between activation and inhibition of the extracellular protease cascade must be tightly regulated to achieve favorable outcomes. Previous studies have shown that serpins—serine protease inhibitors—negatively regulate insect innate immunity by inhibiting extracellular protease cascade signaling. Although the roles of serpins in insect innate immunity are well described, the physiological mechanisms underlying their synergistic effects remain poorly understand. Here, we characterize the molecular mechanism by which serpin-1a and serpin-6 synergistically maintain immune homeostasis of the silkworm Toll pathway under physiological and pathological conditions. Through in vitro biochemical assays and in vivo bioassays, we demonstrate that clip-domain serine protease 2 (CLIP2), as the Toll cascade-activating terminal protease, is responsible for processing proSpätzle1 to induce the expression of antimicrobial peptides. Further biochemical and genetic analyses indicate that constitutively expressed serpin-1a and inducible serpin-6 synergistically target CLIP2 to maintain homeostasis of the silkworm Toll pathway under physiological and pathological conditions. Taken together, this study provides new insights into the precise regulation of Toll cascade activation signals in insect innate immune responses and highlights the importance and complexity of insect immune homeostasis regulation.

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