Role of MIF (Macrophage Migration Inhibitory Factor) proteins in aphids in plant cell death

President of the jury :                       

• Dr Armel Gallet                          ISA, Sophia Antipolis

Rapporteurs :                     

• Dr Lieven de Veylder                 VIB, Belgique
• Dr Federica Calevro                  INRAE/INSA, Lyon                  

Examiners

• Dr Benjamin Gourbal               IHPE, Perpignan
• Dr Fabien Jammes                    ISA, Sophia Antipolis

Thesis Directors :

• Dr Christine Coustau                 ISA, Sophia Antipolis
• Dr Janice de Almeida Engler    ISA, Sophia Antipolis  

Abstract :

Aphids are among the world's most common plant parasites, causing serious damage to agricultural crops. Green peach aphid populations have developed resistance to various regularly used pesticides, necessitating the development of new management techniques. Despite their significant impact on agriculture and food production, the molecular processes underpinning aphid–plant interactions remain largely unknown. Our recent work demonstrates that a macrophage migration inhibitory factor (MIF) is released in aphid saliva during feeding and suppresses host plant immunity by reducing cell death processes. MIFs are crucial pro-inflammatory cytokines conserved across kingdoms. In both vertebrates and invertebrates, MIFs play essential roles in regulating inflammatory responses, cell death, and cell proliferation. To better understand the role of aphid MIFs in the inhibition of plant cell death, we conducted morphological, cellular, molecular, and biochemical analyses to determine how cell death is prevented by aphid MpMIF1 (Myzus persicae MIF1). Microscopic analysis revealed that MpMIF1 preserves cell and organelle morphology while protecting against endoplasmic reticulum and cytoskeletal stress. Gene expression analysis showed that MpMIF1 significantly impacts key genes and proteins involved in cell death and regeneration. To investigate MpMIF1's effect on the DNA Damage Response (DDR), we performed γH2AX immunolocalization (a biomarker for DNA double-strand breaks (DSB)) within plant cells. Our results revealed that MpMIF1 reduces H2AX phosphorylation, thereby decreasing DSB formation in the presence of a cell death inducer. These findings suggest that MpMIF1 may play a critical role in DDR in plants following biotic stress. Moreover, in mammals, MIF proteins are known to negatively regulate p53 and Caspase-3 while activating MAPK signaling pathways. In our system, we found that MpMIF1 negatively affects SOG1 expression (the functional analog of p53) and Caspase-3-like activity (DEVDase) while increasing phosphorylation of MAPK Erk1/2 signaling in plants. Interestingly, similar to the MIF-p53 interaction in mammals, Spit-Luciferase and Co immunoprecipitation assays demonstrated that MpMIF1 physically interacts with the SOG1 protein. Since SOG1 and p53 do not share sequence similarity but perform analogous functions, this result suggests a remarkable conservation of regulatory mechanisms between plants and mammals. These findings provide valuable insights into the effects of aphid MIF on plant immune responses and may facilitate the development of new aphid biocontrol methods.

Keywords :

Cell death, DNA damage, immune response, macrophage migration inhibitory factor (MIF), Myzus persicae, salivary protein, SOG1.

In person or via Zoom: 

https://inrae-fr.zoom.us/j/8869452953?omn=93483651498