Beyond immunity: The Imd pathway as a coordinator of host defense, organismal physiology and behavior

Zhai, Zongzhao; Huang, Xuejun; Yin, Yan

doi:10.1016/j.dci.2017.11.008

Cited by 59 publications

(58 citation statements)

References 137 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Increasing research has emphasized the role of IMD in guiding the conversation between bacteria and host, which may act as a central regulator to integrate host defense, the physiology, and animal behavior of the whole organism (Zhai et al, 2018). The landscape of protein-protein interactions in Drosophila IMD signaling has recently been revealed by the Hoffmann group (Fukuyama et al, 2013).…”

Section: Discussionmentioning

confidence: 99%

Drosophila Histone Demethylase KDM5 Regulates Social Behavior through Immune Control and Gut Microbiota Maintenance

Chen

Luan

Liu

et al. 2019

Cell Host & Microbe

151

143

View full text Add to dashboard Cite

Graphical AbstractHighlights d Deficiency of KDM5 demethylase causes gut dysbiosis and abnormal social behavior in flies d Lactobacillus plantarum administration improves social behavior in kdm5-deficient animals d KDM5 maintains proper immune activity in a transcriptional and microbiota-mediated manner d KDM5 demethylase affects social behavior through the gutmicrobiome-brain axis SUMMARY Loss-of-function mutations in the histone demethylases KDM5A, KDM5B, or KDM5C are found in intellectual disability (ID) and autism spectrum disorders (ASD) patients. Here, we use the model organism Drosophila melanogaster to delineate how KDM5 contributes to ID and ASD. We show that reducing KDM5 causes intestinal barrier dysfunction and changes in social behavior that correlates with compositional changes in the gut microbiota. Therapeutic alteration of the dysbiotic microbiota through antibiotic administration or feeding with a probiotic Lactobacillus strain partially rescues the behavioral, lifespan, and cellular phenotypes observed in kdm5-deficient flies. Mechanistically, KDM5 was found to transcriptionally regulate component genes of the immune deficiency (IMD) signaling pathway and subsequent maintenance of host-commensal bacteria homeostasis in a demethylase-dependent manner. Together, our study uses a genetic approach to dissect the role of KDM5 in the gut-microbiome-brain axis and suggests that modifying the gut microbiome may provide therapeutic benefits for ID and ASD patients.

show abstract

Section: Discussionmentioning

confidence: 99%

Drosophila Histone Demethylase KDM5 Regulates Social Behavior through Immune Control and Gut Microbiota Maintenance

Chen

Luan

Liu

et al. 2019

Cell Host & Microbe

151

143

View full text Add to dashboard Cite

show abstract

“…Our study uncovered cell-specific contributions of IMD to host metabolism, intestinal growth, and survival of enteric infection. IMD has complex roles in the regulation of intestinal anti-bacterial responses (43). In the anterior, IMD activation in differentiated epithelial cells requires detection of cell-extrinsic, polymeric peptidoglycan by PGRP-LC (24).…”

Section: Discussionmentioning

confidence: 99%

Immune Regulation of Intestinal Stem Cell Proliferation and Differentiation in Drosophila

Shin

Ferguson

Willms

et al. 2019

Preprint

View full text Add to dashboard Cite

The intestinal epithelium contains secretory and absorptive cell lineages that develop from undifferentiated progenitor cells. Despite the collective importance of these cells to host responses against microbial invaders, little is known about the contributions of immune responses in individual cell types to the maintenance of intestinal homeostasis. In this study, we asked how inhibition of immune pathway activity exclusively in progenitor cells, or in differentiated enterocytes, affects midgut homeostasis in adult Drosophila. We found that blocking immune activity in enterocytes rendered flies more tolerant of Vibrio cholerae infection, had negligible effects on the gut bacterial microbiome, and significantly affected metabolism. In contrast, inhibition of immune activity in progenitors rendered flies less tolerant of Vibrio infections, modified host association with Lactobacillus symbionts, and blocked growth and renewal in the midgut epithelium. Together, these data uncover substantial cell type-specific contributions of epithelial immunity to adult intestinal homeostasis.

show abstract

“…Relish, Rel) and of the Toll pathway ( i.e . Dorsal, Dl), Cactus (Cact) as well as the secreted protein PGRP-SA (Govind, 1999; Valanne et al, 2011; Zhai et al, 2018) (Table S2) . In addition, it expresses proteins associated with the JNK pathway such as Jra and Puc (Martin-Blanco et al, 1998; Zheng et al, 2017).…”

Section: Resultsmentioning

confidence: 99%

“…The PL-AMP cluster (0.5% of the hemocytes) presents strong similarities with PL-Rel, as they share the same markers related to the Imd pathway ( Figure 2D ), but distinguishes itself by the expression of the antimicrobial peptides (AMP) Cecropin A1 (CecA1), Cecropin A2 (CecA2), Cecropin C (CecC), Attacin-A (AttA), Attacin-B (AttB) and Attacin-D (AttD) (Figure 2D , Table S2 ) as well as of the markers of PL-Pcd cluster Pcd, Ance, CG31431 and CG34296 ( Figure 2D ). The AMP are usually induced and secreted primarily by the fat body after septic wounds that triggers the Imd pathway (Govind, 1999; Zhai et al, 2018). These data suggest that PL-AMP represents activated hemocytes.…”

Section: Resultsmentioning

confidence: 99%

Temporal specificity and heterogeneity of the fly immune cells’ transcriptional landscape

Cattenoz

Sakr

Pavlidaki

et al. 2019

Preprint

View full text Add to dashboard Cite

Summary Immune cells provide defense against the non-self, however recent data suggest roles well beyond innate immunity, in processes as diverse as development, metabolism and tumor progression. Nevertheless, the heterogeneity of these cells remains an open question. Using bulk RNA sequencing we find that the Drosophila immune cells (hemocytes) display distinct features in the embryo, a closed and rapidly developing system, compared to the larva, which is exposed to environmental and metabolic challenges. Through single cell RNA sequencing we identify fourteen hemocyte clusters present in unchallenged larvae and associated with distinct cellular processes e.g. proliferation, phagocytosis, metabolic homeostasis and humoral response. Finally, we characterize the changes occurring in the hemocyte clusters upon wasp infestation that triggers the differentiation of a novel cell type, the lamellocyte. This first molecular atlas provides precious insights and paves the way to study the biology of the Drosophila immune cells in physiological and pathological conditions.

show abstract

Beyond immunity: The Imd pathway as a coordinator of host defense, organismal physiology and behavior

Cited by 59 publications

References 137 publications

Drosophila Histone Demethylase KDM5 Regulates Social Behavior through Immune Control and Gut Microbiota Maintenance

Drosophila Histone Demethylase KDM5 Regulates Social Behavior through Immune Control and Gut Microbiota Maintenance

Immune Regulation of Intestinal Stem Cell Proliferation and Differentiation in Drosophila

Temporal specificity and heterogeneity of the fly immune cells’ transcriptional landscape

Contact Info

Product

Resources

About