Phagocyte | EPFL Graph Search

vignette|Image au microscope électronique d'un neutrophile (jaune, droite) phagocytant anthrax bacilli (orange, gauche). « Phagocyte » (aussi appelé « cellule phagocytaire ») signifie « cellule mangeuse ». On les appelle parfois éboueurs de l'organisme. Les phagocytes ou « cellules phagocytaires », sont en effet des cellules pouvant ingérer et détruire des particules de taille variable (de l'échelle nanométrique à micrométrique), qui sont par exemple des microbes, des cellules altérées, des tissus sanguins ou des particules étrangères à l'organisme. Les phagocytes jouent un rôle essentiel contre les infections, essentiellement bactériennes, mais ils participent aussi à l'élimination des micro et nanoparticules étrangères qui pénètrent l'organisme. Ils participent aux processus inflammatoires. Le terme « phagocyte » est habituellement utilisé pour les organismes animaux, dont celui de l'être humain, mais des processus comparables à la phagocytose existent chez d'autres organismes viv

Role of Nimrod receptors in the Drosophila melanogaster cellular immune response

Claudia Melcarne

The use of modern molecular biology tools and simple but powerful tractable model organisms such as Drosophila has contributed significantly to our recent advances in the innate immunity field, notably phagocytosis. Since 2001, many phagocytic transmembrane receptors, potential opsonins, and in some cases their ligands, have been discovered. Among them, the Nimrod family, which contains key phagocytic receptors and potential opsonins, deserves special interest as accumulating genetic and biochemical evidence points to their critical role in phagocytosis of both bacteria and apoptotic cells. In this PhD thesis we provided a deeper characterization of two Nimrod transmembrane receptors, Eater and NimC1. In particular, by using single or combined mutations in eater and NimC1, we aimed to further elucidate i) the involvement of each receptor in bacterial phagocytosis and ii) the role of Eater in hemocytes sessility and adhesion. Both receptors have been shown to be specifically expressed in hemocytes, the insect blood cells, and to mediate Gram-positive but not Gram-negative bacteria phagocytosis. In this work we generated a novel NimC1 mutant and demonstrated that the single NimC1 deletion does not affect phagocytosis of bacteria. However, by using the compound NimC1;eater mutant we were able to show that these receptors contribute in a synergistic way to microbes engulfment, but that Eater can bypass the requirement for NimC1. Moreover, we discovered that NimC1, but not Eater, is required for phagocytosis of non-immunogenic particles, namely latex beads and yeast zymosan. Therefore, this work provides evidences of Eater and NimC1 being the main receptors for bacteria phagocytosis, and suggests that those proteins likely play distinct roles in microbial uptake, as tethering and docking receptors. The second part of this thesis re-addresses the role of Eater in hemocyte sessility and adhesion. A previous study showed that this phagocytic receptor is essential to mediate blood cell sessility to the animal integument during larval stages. However, a series of questions about Eater-mediated sessility remains still open. For example, is Eater mediating hemocyte adhesion also in adult flies? And yet, does Eater mediate hemocyte sessility by regulating the expression of cell adhesion genes, therefore functioning as a signalling receptor? By using eater1 mutant adult flies, we showed that, as in larval stages, Eater is required in adult hemocytes to confer adhesion and sessility. Interestingly, we uncovered a potential role of sessility in hemocyte survival during adulthood, since eater1 flies have a decreased number of blood cells. Preliminary transcriptomics analysis led us to hypothesise that this receptor might not work as a signalling molecule, but rather as an adhesion protein providing the initial hemocyte contact to its target surface. In line with Eaterâs role as an adhesion molecule, its over-expression in hemocytes leads to the formation of enlarged cells compared to control. To conclude, this thesis extended our knowledge on the Drosophila cellular immune response, by providing new insights on two Nimrod phagocytic receptors.

EPFL2020

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

Andrew Jonathan Bretscher, Jan Paul Dudzic, Bruno Lemaitre, Claudia Melcarne, Elodie Julie Virginie Ramond

Eater and NimC1 are transmembrane receptors of the Drosophila Nimrod family, specifically expressed in haemocytes, the insect blood cells. Previous ex vivo and in vivoRNAi studies have pointed to their role in the phagocytosis of bacteria. Here, we have created a novel NimC1 null mutant 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 it is not required for haemocyte 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 haemocytes. Surprisingly, NimC1 deletion did not impair phagocytosis of bacteria, nor their adhesion to the haemocytes. However, phagocytosis of both types of bacteria was almost abolished in NimC1(1);eater(1) haemocytes. 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.

WILEY2019

Role of Nimrod receptors in the Drosophila melanogaster cellular immune response

Claudia Melcarne

EPFL2020