The Tripartite Interaction of Host Immunity- Bacillus thuringiensis Infection-Gut Microbiota

Abstract

Bacillus thuringiensis (Bt) is an important cosmopolitan bacterial entomopathogen, which produces various protein toxins that have been expressed in transgenic crops. The evolved molecular interaction between the insect immune system and gut microbiota is changed during the Bt infection process. The host immune response, such as the expression of induced antimicrobial peptides (AMPs), the melanization response, and the production of reactive oxygen species (ROS), varies with different doses of Bt infection. Moreover, B. thuringiensis infection changes the abundance and structural composition of the intestinal bacteria community. The activated immune response, together with dysbiosis of the gut microbiota, also has an important effect on Bt pathogenicity and insect resistance to Bt. In this review, we attempt to clarify this tripartite interaction of host immunity, Bt infection, and gut microbiota, especially the important role of key immune regulators and symbiotic bacteria in the Bt killing activity. Increasing the effectiveness of biocontrol agents by interfering with insect resistance and controlling symbiotic bacteria can be important steps for the successful application of microbial biopesticides.

Keywords: Bacillus thuringiensis; antimicrobial peptide; gut microbiota.

Figure 1

The tripartite interaction model between host immunity, Bt (Bacillus thuringiensis) infection, and gut microbiota.

Figure 2

Insect gut immunity protects against infections and maintains gut microbiota homeostasis. DAP-type peptidoglycan (PGN) from intestinal bacteria is sensed by PGRP-LC, which triggers the IMD-dependent MEKK1-MKK3-p38 DUOX-expression pathway. Uracil also activates MEKK1-MKK3-p38 in a PLCβ-dependent manner; the activation of p38 enhances the transactivating function of ATF, which in turn activates the transcription of dual oxidase (DUOX). On the other hand, PLCβ-calcium signaling is responsible for the induction of DUOX enzymatic activity. Both contribute to the production of reactive oxygen species (ROS) in the gut lumen, where they control endogenous and infectious bacteria [64]. DAP-type PGN recognition by PGRP-LC also triggers the IMD pathway through the translocation of the nuclear factor-κB (NF-κB) family member Relish, which then induces increased transcription of antimicrobial peptides (AMPs) genes [23]. Besides, the IMD pathway has established a negative feedback loop to prevent overactivation. One is the members of the PGRP family gene (PGRP-LB or PGRP-SC) with amidase activity can cleave PGN and therefore blocks the activation of the IMD pathway. Another is Pirk, which interferes with the plasma membrane localization of PGRP-LC [62]. In some insect species, the Toll signaling pathway is activated with the Lys-type PGN recognition by PGRP-SA or PGRP-SD after microbial infection. This initiates a proteolytic cascade that ultimately cleaves pro-Spatzle into an active ligand for Toll, leading to the activation of the NF-κB-like transcription factors dorsal and then translocation into the nucleus to induce increased transcription of the AMP gene. Finally, these immune regulatory networks cooperatively help to maintain gut homeostasis.