Transfer of Immunity from Mother to Offspring Is Mediated via Egg-Yolk Protein Vitellogenin

Abstract

Insect immune systems can recognize specific pathogens and prime offspring immunity. High specificity of immune priming can be achieved when insect females transfer immune elicitors into developing oocytes. The molecular mechanism behind this transfer has been a mystery. Here, we establish that the egg-yolk protein vitellogenin is the carrier of immune elicitors. Using the honey bee, Apis mellifera, model system, we demonstrate with microscopy and western blotting that vitellogenin binds to bacteria, both Paenibacillus larvae – the gram-positive bacterium causing American foulbrood disease – and to Escherichia coli that represents gram-negative bacteria. Next, we verify that vitellogenin binds to pathogen-associated molecular patterns; lipopolysaccharide, peptidoglycan and zymosan, using surface plasmon resonance. We document that vitellogenin is required for transport of cell-wall pieces of E. coli into eggs by imaging tissue sections. These experiments identify vitellogenin, which is distributed widely in oviparous species, as the carrier of immune-priming signals. This work reveals a molecular explanation for trans-generational immunity in insects and a previously undescribed role for vitellogenin.

Vitellogenin in inflammation and immunity in social insects

“…However, insects lack antibodies. We have shown that vitellogenin is a carrier of immunological memory from one generation to the next in the honey bee [42] . Vitellogenin attaches to pathogenic pattern molecules and carries them to eggs in the queen ovaries [42] .…”

“…We have shown that vitellogenin is a carrier of immunological memory from one generation to the next in the honey bee [42] . Vitellogenin attaches to pathogenic pattern molecules and carries them to eggs in the queen ovaries [42] . This combined role in pathogen recognition and egg-yolk formation provides a mechanism for transgenerational immune priming in insects, although this finding awaits for confirmation in other species.…”

“…Piscine vitellogenin gene expression is upregulated upon infection -the protein recognizes bacterial and fungal surface components, and facilitates phagocytosis of the pathogens [38] . Using the honey bee as a model, we have shown that insect vitellogenin shares most of the immunological properties identified in fish; honey bee vitellogenin binds to the Gram negative E. coli and the Gram positive honey bee pathogen Paenibacillus larvae, and, more specifically, to the pathogen-associated pattern molecules lipopolysaccharide, peptidoglycan and yeast zymosan [42] .…”

Early gut colonizers shape parasite susceptibility and microbiota composition in honey bee workers

“…As social insects, they form colonies with tens of thousands of mostly nonreproductive female workers that progressively perform a variety of tasks required for colony maintenance and growth as they age. This division of labor is centrally regulated by the expression of vitellogenin (Vg), a gene under strong positive selection in workers (12,13) encoding a glycolipoprotein that affects development, lifespan, and immunity (14)(15)(16)(17)(18) and serves as a key biomarker for bee health and fitness (13,(19)(20)(21).…”

Genes Underlying Reproductive Division of Labor in Termites, with Comparisons to Social Hymenoptera

“…In addition, in social Hymenoptera Vgs have much broader social functions. In the honeybee, Vgs are, for instance, involved in division of labor among workers (forager vs. nurse bees, pollen vs. nectar foragers), in aging or in immune priming (e.g., Seehuus et al, 2006;Nelson et al, 2007;Page and Amdam, 2007;Rascon et al, 2011;Salmela et al, 2015). In ants, they can be differentially expressed between castes (e.g., Gräff et al, 2007;Feldmeyer et al, 2014) and also regulate maternal effects on polyphenism .…”