Deciphering bat influenza H18N11 infection dynamics in male Jamaican fruit bats on a single-cell level

Jamaican fruit bats ( Artibeus jamaicensis ) naturally harbor a wide range of viruses of human relevance. These infections are typically mild in bats, suggesting unique features of their immune system. To better understand the immune response to viral infections in bats, we infected male Jamaican fruit bats with the bat-derived influenza A virus (IAV) H18N11. Using comparative single-cell RNA sequencing, we generated single-cell atlases of the Jamaican fruit bat intestine and mesentery. Gene expression profiling showed that H18N11 infection resulted in a moderate induction of interferon-stimulated genes and transcriptional activation of immune cells. H18N11 infection was predominant in various leukocytes, including macrophages, B cells, and NK/T cells. Confirming these findings, human leukocytes, particularly macrophages, were also susceptible to H18N11, highlighting the zoonotic potential of this bat-derived IAV. Our study provides insight into a natural virus-host relationship and thus serves as a fundamental resource for future in-depth characterization of bat immunology. Here, Kessler et al use single-cell RNA sequencing of the intestine and mesentery from H18N11 influenza-infected bats to show that viral infection is predominant in leukocytes and causes activation of immune cells and antiviral gene signatures.