Intergenerational inheritance of trained immunity and heterologous resistance to infections (RRBS - DNA methylation)

Intergenerational inheritance (Inter-I) of phenotypic characteristics has been demonstrated in plants and invertebrates, with epigenetic modifications playing a role in the inheritance of a variety of features such as appearance1, adaptation to stress, or resistance to infections. Here we provide evidence of Inter-I of transcriptional and epigenetic signatures of trained immunity to the progeny of mice that survived a sublethal systemic Candida albicans infection. Intergenerational trained mice (F1) presented with significant cellular, developmental, transcriptional, and epigenetic changes within the bone marrow resident myeloid effector and progenitor cell compartment. These alterations led to an enhanced responsiveness to in vivo endotoxin challenge and Escherichia coli infection, providing the offspring with protection against heterologous infections. These results argue for the contribution of Lamarckian evolutionary processes to protect against infections in vertebrates. Overall design: Male mice were infected with subletal dose of C. albicans. One month after clearance of the infection, 'resting' (mock-infected with PBS, F0R) and the 'trained' (C. albicans-infected and recovered, F0T) mice were mated with healthy non-infected females. DNA methylomes of 10 isogenic control males and 10 infected and recovered males using a comprehensive HaeIII restriction based RRBS (reduced representation bisulfite sequencing) approach.