Many encapsulated bacteria use capsules to cause invasive diseases. However, it remains largely unknown how the capsules enhance bacterial virulence under in vivo infection conditions. Here we show that the capsules primarily target the liver to enhance bacterial survival at the onset of blood-borne infections. In a mouse sepsis model, the capsules enabled human pathogens Streptococcus pneumoniae and Escherichia coli to circumvent the recognition of liver-resident macrophage Kupffer cells (KCs) in a capsular serotype-dependent manner. In contrast to effective capture of acapsular bacteria by KCs, the encapsulated bacteria are partially (low-virulence types) or completely (high-virulence types) “untouchable” for KCs. We finally identified the asialoglycoprotein receptor (ASGR) as the first known capsule receptor on KCs to recognize the low-virulence serotype-7F and -14 pneumococcal capsules. Our data identify the molecular interplay between the capsules and KCs as a master controller of the fate and virulence of encapsulated bacteria, and suggest that the interplay is targetable for therapeutic control of septic infections.

Autophagy is a central pathway involved in maintaining cellular homeostasis during development, metabolism, and regeneration. The selective autophagy receptor p62/SQSTM1 is a multifunctional protein that plays a critical role in regulating autophagic activity by interacting with LC3/Atg8 proteins and ubiquitinated substrates. Aedes albopictus has rapidly spread worldwide and poses a serious threat to human health by transmitting dengue and other arboviral diseases. In the present study, we identified a putative p62/SQSTM1 homolog protein (AaSQSTM1) in Ae. albopictus, which contains conserved structural regions, including the Atg8 family interaction motif (AIM) and ubiquitin-associated (UBA) domain. The expression levels of AaSQSTM1 and AaAtg8 varied from the egg stage to the adult stage in Ae. albopictus. Quantitative analyses revealed that blood-feeding upregulated the expression levels of AaSQSTM1 and AaAtg8 in the ovaries of female adults. AaSQSTM1 was applied to monitor autophagic activity alone or with AaAtg8 by assaying endogenous protein levels and overexpressing fluorescent reporters in C6/36 cells. Our study revealed that AaSQSTM1 regulates the autophagic activity with AaAtg8, providing a basis for studying the autophagy process in mosquitoes.

Dengue virus (DENV), a member of the Flaviviridae family, poses a significant global public health threat, with an estimated 100–400 million infections annually [1]. As the primary vectors responsi...