Metabolic control of cellular immune-competency by odors in Drosophila
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Abstract
Studies in different animal model systems have revealed the impact of odors on immune cells; however, any understanding on why and how odors control cellular immunity remained unclear. We find that Drosophila employ an olfactory-immune cross-talk to tune a specific cell type, the lamellocytes, from hematopoietic-progenitor cells. We show that neuronally released GABA derived upon olfactory stimulation is utilized by blood-progenitor cells as a metabolite and through its catabolism, these cells stabilize Sima/HIFα protein. Sima capacitates blood-progenitor cells with the ability to initiate lamellocyte differentiation. This systemic axis becomes relevant for larvae dwelling in wasp-infested environments where chances of infection are high. By co-opting the olfactory route, the preconditioned animals elevate their systemic GABA levels leading to the upregulation of blood-progenitor cell Sima expression. This elevates their immune-potential and primes them to respond rapidly when infected with parasitic wasps. The present work highlights the importance of the olfaction in immunity and shows how odor detection during animal development is utilized to establish a long-range axis in the control of blood-progenitor competency and immune-priming.
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###This manuscript is in revision at eLife
The decision letter after peer review, sent to the authors on August 20 2020, follows.
Summary
The reviewers agree that the paper has been improved and is now easier to read. The findings were judged fascinating but there are still issues. The authors delineate a linear story (one pathway) but some elements could affect the system independently. The reviewers agree on a set of recommendations that should be addressed during the revision of the manuscript.
Essential Revisions
- Resistance to parasitoid wasp.
The authors provide an extremely important body of work. However, the reviewers have a concern about the physiological significance of the phenotype. It is appropriate to hypothesize that an increase in lamellocyte production will yield a more potent immune response against parasitoids, as …
###This manuscript is in revision at eLife
The decision letter after peer review, sent to the authors on August 20 2020, follows.
Summary
The reviewers agree that the paper has been improved and is now easier to read. The findings were judged fascinating but there are still issues. The authors delineate a linear story (one pathway) but some elements could affect the system independently. The reviewers agree on a set of recommendations that should be addressed during the revision of the manuscript.
Essential Revisions
- Resistance to parasitoid wasp.
The authors provide an extremely important body of work. However, the reviewers have a concern about the physiological significance of the phenotype. It is appropriate to hypothesize that an increase in lamellocyte production will yield a more potent immune response against parasitoids, as seen in other Drosophila species (i.e. D. suzukii). However, genetic perturbation that increase lamellocyte numbers, or perturbs the immune system in any manner, does not necessarily mean that the immune response mounted will be successful. The authors should provide experiments monitoring resistance to parasitoid wasps when the pathway they discovered is perturbated. The should monitor the impact of feeding larvae on WOF on resistance and how disturbing Or49A, Gat and Ssadh affect resistance to parasitoid wasp.
- RNAi effectivity and using one line.
The reviewers questioned the validity of the study as some results are based only one RNAi and their knockdown efficiencies were tested by using a ubiquitous and not in the actual tissues. They however recognize that the model is supported by the fact that they are testing different players affect the pathway. The reviewers however ask to repeat the experiments with Gat and Ssadh using another RNAi line to reinforce their conclusion.
- Sima staining.
Figure 3: There are discrepancies in the Sima staining which put question into the specificity of this staining/back ground. For example, some LGs showed a punctate expression of Sima in the posterior part of the LG (Fig 3f, g, and h which is not seem in the other LGs). Pictures in Fig3b, k and m are not in agreement with quantifications in 3o. The same comment holds for Fig 3f-I and quantifications in j. Expression of Sima in lamellocyte is also not convincing. The specificity of the Sima antibody has to be checked. Sup Fig 7B is the difference in sima mRNA levels significant? The reviewers recommend to address this point or at least to prepare a supplementary figure showing replicated of the picture they use of their graph.
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