C-type lectin-mediated microbial homeostasis is critical for Helicoverpa armigera larval growth and development

The immune system of a host functions critically in shaping the composition of the microbiota, and some microbes are involved in regulating host endocrine system and development. However, whether the immune system acts on endocrine and development by shaping the composition of the microbiota remains unclear, and few molecular players or microbes involved in this process have been identified. In the current study, we found that RNA interference of a C-type lectin (HaCTL3) in the cotton bollworm Helicoverpa armigera suppresses ecdysone and juvenile hormone signaling, thus reducing larval body size and delaying pupation. Depletion of HaCTL3 also results in an increased abundance of Enterocuccus mundtii in the hemolymph, which may escape from the gut. Furthermore, HaCTL3 and its controlled antimicrobial peptides (attacin, lebocin, and gloverin) are involved in the clearance of E. mundtii from the hemolymph via phagocytosis or direct bactericidal activity. Injection of E. mundtii into larval hemocoel mimics HaCTL3-depleted phenotypes and suppresses ecdysone and juvenile hormone signaling. Taken together, we conclude that HaCTL3 maintains normal larval growth and development of H. armigera via suppressing the abundance of E. mundtii in the hemolymph. Our results provide the first evidence of an immune system acting on an endocrine system to modulate development via shaping the composition of microbiota in insect hemolymph. Thus, this study will deepen our understanding of the interaction between immunity and development. Author summary Considering that a large number of hemocytes and multiple soluble effectors are present in insect hemolymph, it is conventionally believed that healthy insect hemolymph is a hostile environment for bacteria and is, therefore, sterile. However, increasing evidences disprove this opinion, although the interactive mechanism between hemolymph microbiota and insect host, as well as the function of hemolymph microbiota, remain unclear. C-type lectin (CTL), as pattern recognition receptor (PRR), plays important roles in defending against various pathogens. Here we found that various bacteria colonized the hemolymph of the cotton bollworm Helicoverpa armigera. We first reported that an H. armigera CTL (HaCTL3) was involved in modulating larval growth and development. Further study indicated that HaCTL3-mediated homeostasis of Enterocuccus mundtii in the hemolymph is critical for normal larval growth and development. Our study demonstrated that this PRR modulated insect development through shaping hemolymph microbiota, which may represent a novel mechanism of immune system regulation during insect development.