Targeting symbionts by apolipoprotein L proteins modulates gut immunity

Area of Science:

• Microbiome research
• Immunology
• Host-microbe interactions

Background:

• Mammalian gut microbiota interact with hosts via bioactive molecules.
• Host strategies for benefiting from symbiotic relationships are underexplored.

Purpose of the Study:

• To investigate host-secreted factors that mediate beneficial gut symbiotic relationships.
• To identify mechanisms by which the host benefits from commensal bacteria.

Main Methods:

• Flow cytometry sorting of APOL9-binding bacteria.
• 16S ribosomal RNA gene sequencing (APOL9-seq).
• Genetic manipulation of bacterial ceramide-1-phosphate synthesis.

Main Results:

• Mouse enterocytes secrete APOL9a/b, which specifically coat Bacteroidales bacteria via ceramide-1-phosphate (Cer1P) lipids.
• APOL9a/b coating induces outer membrane vesicle (OMV) production from bacteria.
• Bacteroides-derived OMVs enhance host interferon-γ signaling and major histocompatibility complex class II expression.

Conclusions:

• Host-secreted APOL9a/b promotes gut immunological homeostasis by targeting bacterial Cer1P.
• APOL9a/b-mediated OMV production enhances host immune barrier function.
• Loss of APOL9a/b compromises immune function, increasing susceptibility to pathogens.