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Ando, I.

Publications and source records attributed to Ando, I..

4 recordsLinked to original sources

Retracing the horizontal transfer of a novel innate immune factor in Drosophila

Immune systems are among the most dynamically evolving traits across the tree of life, and long-lived macroparasites play an outsized role in shaping animal immunity. Even without adaptive immunity, insects have evolved potent innate immune strategies to neutralize such enemies, including nematodes and parasitoid wasps. One such strategy relies on endosymbioses between insects and toxin-expressing bacteria. Here, we use genome editing in Drosophila melanogaster to retrace the evolution of two of such toxins -- cytolethal distending toxin B (cdtB) and apoptosis inducing protein of 56kDa (aip56) -- that were horizontally transferred from bacteriophages to insects. We found that a cdtB::aip56 fusion gene (fusionB), which is conserved in Drosophila ananassae subgroup species, dramatically promoted fly survival and suppressed wasp development when expressed in D. melanogaster immune tissues. FusionB, a functional nuclease, was secreted into the host hemolymph where it targeted the parasitoid embryos serosal tissue and is to our knowledge the first humoral anti-parasitoid toxin in Drosophila. When expressed ubiquitously, fusionB slowed development in late stage fly larvae and eventually killed flies, pointing to the salience of regulatory constraint in preventing autoimmunity. Our findings demonstrate how horizontal gene transfer, in the right regulatory context, can instantly provide new and potent innate immune modules in animals.

evolutionary biology↗

Regression plane concept: analysing continuous cellular processes with machine learning

Biological processes are inherently continuous, and the chance of phenotypic discovery is significantly restricted by discretising them. Using multi-parametric active regression we introduce a novel concept to describe and explore biological data in a continuous manner. We have implemented Regression Plane (RP), the first user-friendly discovery tool enabling class-free phenotypic supervised machine learning.

bioinformatics↗

Multi-Dimensional Immuno-Profiling of Drosophila Hemocytes by Single Cell Mass Cytometry

Single cell mass cytometry (SCMC) combines features of traditional flow cytometry (FACS) with mass spectrometry and allows the measurement of several parameters at the single cell level, thus permitting a complex analysis of biological regulatory mechanisms. We optimized this platform to analyze the cellular elements, the hemocytes, of the Drosophila innate immune system. We have metal-conjugated six antibodies against cell surface antigens (H2, H3, H18, L1, L4, P1), against two intracellular antigens (3A5, L2) and one anti-IgM for the detection of L6 surface antigen, as well as one anti-GFP for the detection of crystal cells in the immune induced samples. We investigated the antigen expression profile of single cells and hemocyte populations in naive, in immune induced states, in tumorous mutants (hopTum bearing a driver mutation and l(3)mbn1 carrying deficiency of a tumor suppressor) as well as in stem cell maintenance defective hdc{Delta}84 mutant larvae. Multidimensional analysis enabled the discrimination of the functionally different major hemocyte subsets, lamellocytes, plasmatocytes, crystal cell, and delineated the unique immunophenotype of the mutants. We have identified sub-populations of L2+/P1+ (l(3)mbn1), L2+/L4+/P1+ (hopTum) transitional phenotype cells in the tumorous strains and a sub-population of L4+/P1+ cells upon immune induction. Our results demonstrated for the first time, that mass cytometry, a recent single cell technology combined with multidimensional bioinformatic analysis represents a versatile and powerful tool to deeply analyze at protein level the regulation of cell mediated immunity of Drosophila.

immunology↗

Two Nimrod receptors, NimC1 and Eater, synergistically contribute to bacterial phagocytosis in Drosophila melanogaster

Eater and NimC1 are transmembrane receptors of the Drosophila Nimrod family, specifically expressed in hemocytes, the insect blood cells. Previous ex vivo and in vivo RNAi studies have pointed to their role in the phagocytosis of bacteria. Here, we have created a novel null mutant in NimC1 to re-evaluate the role of NimC1, alone or in combination with Eater, in the cellular immune response. We show that NimC1 functions as an adhesion molecule ex vivo, but in contrast to Eater is not required for hemocyte sessility in vivo. Ex vivo phagocytosis assays and electron microscopy experiments confirmed that Eater is the main phagocytic receptor for Gram-positive, but not Gram-negative bacteria, and contributes to microbe tethering to hemocytes. Surprisingly, the NimC1 deletion did not impair phagocytosis of bacteria, nor their adhesion to the hemocytes. However, phagocytosis of both types of bacteria was almost abolished in NimC11;eater1 hemocytes. This indicates that both receptors contribute synergistically to the phagocytosis of bacteria, but that Eater can bypass the requirement for NimC1. Finally, we uncovered that NimC1, but not Eater, is essential for uptake of latex beads and zymosan particles. We conclude that Eater and NimC1 are the two main receptors for phagocytosis of bacteria in Drosophila, and that each receptor likely plays distinct roles in microbial uptake.

immunology↗