Leishmania major drives host phagocyte death and cell-to-cell transfer depending on intracellular pathogen proliferation rate.

The virulence of intracellular pathogens relies largely on the ability to survive and replicate within phagocytes but also on release and transfer into new host cells. Such cell-to-cell transfer could represent a target for counteracting microbial pathogenesis. However, our understanding of the underlying cellular and molecular processes remains woefully insufficient. Using intravital 2-photon microscopy of caspase-3 activation in the Leishmania major-infected (L. major-infected) live skin, we showed increased apoptosis in cells infected by the parasite. Also, transfer of the parasite to new host cells occurred directly without a detectable extracellular state and was associated with concomitant uptake of cellular material from the original host cell. These in vivo findings were fully recapitulated in infections of isolated human phagocytes. Furthermore, we observed that high pathogen proliferation increased cell death in infected cells, and long-term residency within an infected host cell was only possible for slowly proliferating parasites. Our results therefore suggest that L. major drives its own dissemination to new phagocytes by inducing host cell death in a proliferation-dependent manner.

The specific expression patterns of sensory neuron membrane proteins are retained throughout the development of the desert locust Schistocerca gregaria.

The desert locust Schistocerca gregaria detects odorants through olfactory sensory neurons (OSNs) that are surrounded by non-neuronal support cells (SCs). OSNs and SCs are housed in cuticle structures, named sensilla found abundantly on the antenna in all developmental stages of the hemimetabolic insect. In insects, multiple proteins expressed by OSNs and SCs are indicated to play a pivotal role in the detection of odorants. This includes insect-specific members of the CD36 family of lipid receptors and transporters called sensory neuron membrane proteins (SNMPs). While the distribution pattern of the SNMP1 and SNMP2 subtypes in OSNs and SCs across different sensilla types has been elucidated for the adult S. gregaria antenna, their localization in cells and sensilla of different developmental stages is unclear. Here, we determined the SNMP1 and SNMP2 expression topography on the antenna of the first, third and fifth instar nymphs. Through FIHC experiments we found that in all developmental stages SNMP1 is expressed in OSNs and SCs of the trichoid and basiconic sensilla while SNMP2 is restricted to the SCs of the basiconic and coeloconic sensilla thus resembling the adult arrangement. Our results demonstrate that both SNMP types have defined cell- and sensilla-specific distribution patterns established already in the first instar nymphs and retained into the adult stage. This conserved expression topography underlines the importance of SNMP1 and SNMP2 in olfactory processes throughout the development of the desert locust.