The C/EBPß-SESN2 Axis Promotes M2b Macrophage Polarization Induced by T.cp-MIF to Suppress Inflammation in Thelazia Callipaeda Infection.

Infection by the conjunctival sucking nematode Thelazia callipaeda results in ocular inflammation and immune impairment. T.cp-MIF, a macrophage migration inhibitor factor of T. callipaeda, can induce macrophage polarization and is involved in the host innate immune response, but little is known about the regulatory mechanisms and the actual immune effect. Understanding the immunoregulatory mechanisms carries significant clinical relevance for the development of novel preventative and therapeutic strategies. The macrophages were induced by T.cp-MIF in vitro, and the polarization direction at different times and the expression of inflammatory factors were detected by flow cytometry analysis, qPCR and western blotting. The key transcription factors and target genes were screened through transcriptome data, and the functions of transcription factors were verified by inhibition experiments in vitro. T.cp-MIF and T. callipaeda adult worms can cause inflammation of the ocular conjunctiva and macrophage infiltration. T.cp-MIF activated macrophages presenting M2b polarization after 48 h and played a role in inhibiting inflammation. Furthermore, based on the results of transcriptome data analysis and inhibition experiments, we demonstrate that this polarization is dependent on the involvement of the transcription factor C/EBPß and its target gene SESN2. Our results demonstrated that the C/EBPß-SESN2 axis plays an important regulatory role in T.cp-MIF-induced macrophage M2b polarization and it provides a new perspective for understanding the immune escape of ocular parasite infection.

The species and abundance of gut bacteria both positively impact Phortica okadai behavior.

BACKGROUND: Gut bacteria, which serve as essential modulators, exert a significant impact on insect physiology and behavior and have substantial application potential in pest management. The dynamics of gut bacteria and their impact on Phortica okadai behavior remain unclear. METHODS: In this study, the dynamics of gut bacteria at different developmental stages in P. okadai were analyzed using 16S ribosomal RNA (rRNA) gene sequencing, and the species and abundance of gut bacteria that affect host behavior were examined via behavioral experiments. RESULTS: A total of 19 phyla, 29 classes, 74 orders, 101 species, and 169 genera were identified. The results of the behavioral experiments indicated that the species Lactiplantibacillus argentoratensis, Acetobacter tropicalis, Leuconostoc citreum, and Levilactobacillus brevis effectively influenced the feeding preference of P. okadai, and the single-bacterium-seeded P. okadai exhibited feeding preferences distinct from those of the germ-free (GF) and wild-type P. okadai. CONCLUSIONS: The species and relative abundance of gut bacteria together positively impact P. okadai behavior. Lactiplantibacillus argentoratensis, as the most attractive bacteria to P. okadai, presents opportunities for novel pest control strategies targeting this vector and agricultural pest.

Dynamic changes in human THP-1-derived M1-to-M2 macrophage polarization during Thelazia callipaeda MIF induction.

Macrophages are innate immune cells with essential roles in the immune response during helminth infection. Particularly, the direction of macrophage polarization could contribute to pathogen trapping and killing as well as tissue repair and the resolution of type 2 inflammation. This study establishes that the recombinant protein of Thelazia callipaeda macrophage migration inhibitory factor (T.cp-MIF) induces THP-1-derived macrophages to undergo M1 to M2 type dynamic polarization, using the methods of flow cytometry, real-time quantitative PCR, differential transcriptomic analysis and western blot. Interestingly, there was an increase in protein and mRNA expression of M1-type proteins and cytokines after the use of PI3K inhibitors, suggesting that the polarization state tends to favor the M1 type after M2 type inhibition. In conclusion, the dynamic polarization mechanism of T.cp-MIF-induced human THP-1-derived macrophages from M1 to M2 type is related to the binding of TLR4. It can first affect the M1 type polarization of macrophages by activating its downstream NF-κB pathway. Activation of the PI3K/Akt pathway and inhibition of NF-κB phosphorylation affects the M2 type polarization of macrophages.