The horticulture and urban entomology research team has been awarded for the regulation of insect gut microbial homeostasis...

Nanhu News Network News (correspondent Yao Zhichao Zhang Zhenyu) Recently, the research results of Professor Zhang Hongyu's team in the College of Plant Science and Technology and the Key Laboratory of Horticultural Plant Biology of the Ministry of Education of our university are "Compartmentalized PGRP expression along the Dipteran Bactrocera dorsalis gut forms a zone of protection for symbiotic.
" bacteria" was published
in Cell Reports.
From the perspective of intestinal regionalization, the study revealed the molecular mechanism
of Imd immune signaling pathway to maintain high immune activity against foreign pathogens while protecting beneficial commensal bacteria in the intestine.

Almost all metazoans inhabit a large number of microorganisms in the intestines, among which intestinal commensal bacteria provide nutrients for the host, promote the digestion and absorption of nutrients, and regulate host behavior and play an important physiological role
.
However, as an important interface between the host and the outside world, the intestine faces many challenges from the external environment, such as the invasion
of pathogenic bacteria.
Therefore, in such a complex environment, the mechanism of action of how the intestinal immune system of insects can effectively remove foreign microorganisms while protecting the beneficial commensal bacteria of the intestine is still unknown
.

The study combined microbiome and transcriptomics to find that there was a regional distribution of beneficial commensal bacteria in the intestines of adult fruit flies, mainly distributed in the anterior part of the midgut.
The imd signaling pathway immune gene also has the phenomenon of regionalized expression, and the intestinal regionalized expression of peptidoglycan recognition receptor (PGRPs) family gene matches
the regionalized distribution of intestinal commensal bacteria.
Among them, the regional expression of PGRP-LB and PGRP-SB genes was positively correlated with the regionalized distribution of commensal bacteria, while the regionalized expression of PGPRP-LC gene and its mediated antimicrobial peptide genes (AMPs) was negatively correlated
with the regionalized distribution of commensal bacteria.

The authors used RNAi technology to find that PGRP-LB and PGRP-SB genes were the main negative regulatory genes of the intestinal Imd signaling pathway of the orange fruit fly, and the silencing of PGRP-LB and PGRP-SB genes would induce up-regulation of the AMPs gene expression in the AMG segment, thereby disrupting the homeostatic balance of the host intestinal microbial community, significantly reducing the intestinal commensal bacteria and significantly increasing
the minor flora.
When the silencing effect of the PGRP-LB and PGRP-SB genes disappeared, the disturbed gut microbiome also returned to normal levels
.

PGPR-LC gene and its mediated AMPs gene are highly expressed in the foregut play an important role
in host immune defense.
Feeding Providencia rettgeri can significantly induce up-regulated expression
of foregut PGPR-LC and AMPs genes.
The downregulation of AMPs genes caused by the silencing of PGPR-LC gene in the foregut impairs the ability of the Imd signaling pathway to remove foreign pathogens, resulting in P.
in the foregut and midgut.
The bacterial load of rettgeri is significantly increased, which in turn disrupts the homeostasis of intestinal commensal bacteria in the anterior midgut, resulting in a decrease
in the intestinal commensal bacterial load in this segment.

Based on the above conclusions, the authors propose a regulatory network model in which the Imd immune signaling pathway provides a protection zone for intestinal commensal bacteria, that is, the regionally expressed PGRPs gene regulates the intestinal regionalization expression of Imd signaling pathway effector gene AMPs, which effectively protects against foreign pathogenic bacteria through high expression in the foregut, and provides a "protection zone"
for the stable colonization of intestinal commensal bacteria at low levels in the foregut and midgut 。 This study elucidates the molecular mechanism of how the Imd signaling pathway can effectively defend against foreign pathogens while tolerating intestinal commensal microorganisms through intestinal regionalization, in order to reveal the mechanism
of how the immune system maintains the homeostatic balance of host gut microbes.

The Imd pathway PGPRs family gene establishes a "protected area" for intestinal commensal bacteria

Yao Zhichao, postdoctoral fellow of Huazhong Agricultural University, is the first author of the paper, Professor Zhang Hongyu is the corresponding author, the team has graduated Dr.
Cai Zhaohui, doctoral student Bai Shuai, graduate students Ma Qiongke, Wang Yichen, Zhang Ping, Guo Qiongyu, Gu Jian, and Professor Bruno Lemaitre of the Swiss Federal Institute of Technology in Lausanne participated in some of the research work
。 Professor Marcelo Jacobs-Lorena of Johns Hopkins University in the United States, Dr.
Michael Ben-Yosef of the Israel Center for Agricultural Research, the team Professor Li Xiaoxue and Ms.
Hannah Westlake of the Swiss Federal Institute of Technology in Lausanne helped
.
This study was supported by the National Natural Science Foundation of China (Nos.
31872931, 31801744 and 31572008) and the National Modern Agricultural Industrial Technology System (No.
CARS-26).

Reviewed by: Hongyu Zhang

【English Summary】

l All metazoan guts are subject to opposing pressures wherein the immune system must eliminate pathogens while tolerating the presence of symbiotic microbiota.
 The Imd pathway is essential to defense against invading pathogens in insect guts, but tolerance mechanisms are less understood.

l Herein, by using high throughput sequencing and qPCR, we find that symbiotic bacteria are mainly located in the anterior midgut (AMG) of Bactrocera dorsalis, and their spatial distribution in different gut regions perfectly matches the expression profiles of PGRP-LB and PGRP-SB, two PGRP genes that negatively regulate the Imd pathway of B.
dorsalis.
Both PGRP-LB and PGRP-SB in the midgut restrain host’s immune response to provide a protective zone for symbiotic bacteria.
Consistent with this, knock-down of PGRP-LB and PGRP-SB enhances the expression of antimicrobial peptide genes and reduces Enterobacteriaceae numbers while increasing abundance of opportunistic pathogens.
 Microbiota numbers recover to normal levels after the RNAi effect subsided.
In contrast, high expression of PGRP-LC in the foregut allows increased antibacterial peptide production to efficiently filter the entry of pathogens, silencing the Imd pathway receptor gene PGRP-LC increases colonization by the opportunistic pathogen Providencia rettgeri, which ultimately overtakes the AMG and disrupts the microbiota.

l Taken together, our study describes a mechanism by which regional expression of PGRPs construct a protective zone for symbiotic microbiota while maintaining the ability to fight pathogens.

Link to paper: