Host generated nitric oxide (NO), derived from inducible nitric oxide synthase (iNOS), has an established role in modulating immunity to control diverse infections, including infection with Mycobacterium tuberculosis (Mtb). High concentrations of NO are produced by macrophages in response to pathogen-associated molecular patterns, usually in combination with IFNg produced by innate and/or adaptive effector lymphocytes. Caspase-11 is a pro-inflammatory protease best known for its role in sensing intracellular LPS and activating the non-canonical inflammasome. Here, we present data which identifies a novel role for caspase-11 during macrophage defence against Mtb. Caspase-11 deficient bone marrow derived macrophages (Casp11-/- BMDM) have enhanced levels of Mtb infection in vitro, when compared to wild-type (WT) BMDM. We show that caspase-11 boosts iNOS expression and NO production in WT BMDM. Treatment of Casp11-/- BMDM with the NO donor, DETA-NO, reduces Mtb infection levels to similar levels as those observed in WT BMDM. Our data propose an additional role for caspase-11 during host defence and provide novel insight into the regulation of iNOS expression during infection.

Host generated nitric oxide (NO), derived from inducible nitric oxide synthase (iNOS), has an established role in modulating immunity to control diverse infections, including infection with _Mycobacterium tuberculosis_ (_Mtb_). High concentrations of NO are produced by macrophages in response to pathogen-associated molecular patterns, usually in combination with IFNg produced by innate and/or adaptive effector lymphocytes. Caspase-11 is a pro-inflammatory protease best known for its role in sensing intracellular LPS and activating the non-canonical inflammasome. Here, we present data which identifies a novel role for caspase-11 during macrophage defence against _Mtb_. Caspase-11 deficient bone marrow derived macrophages (_Casp11-/-_ BMDM) have enhanced levels of _Mtb_ infection _in vitro_, when compared to wild-type (WT) BMDM. We show that caspase-11 boosts iNOS expression and NO production in WT BMDM. Treatment of _Casp11-/-_ BMDM with the NO donor, DETA-NO, reduces _Mtb_ infection levels to similar levels as those observed in WT BMDM. Our data propose an additional role for caspase-11 during host defence and provide novel insight into the regulation of iNOS expression during infection.

Novel role for caspase-11 in host defence against Mycobacterium tuberculosis.

Exploring the intricacies of host-pathogen communication is vital in order to understand why
some microbes persist within a host, while others are effectively cleared. As such,
host-pathogen communication is an urgent area of research underpinning human health
and disease, especially given the emerging concerns of antibiotic resistance.
Understanding host-pathogen pathways requires intricate knowledge in the fields of both
microbiology and immunology.

Living in a world of specialists, where scientists sometimes invest their whole career
studying one organism, a specific pathway or a protein, multidisciplinary discussions of
host-pathogen interactions are highly needed. This international conference will provide
such a forum for scientific exchange at the highest level, between scientists from different
research areas related to host-pathogen interactions, with the aim to trigger fruitful
collaborations addressing the urgent questions in the field.

This meeting has an additional special focus of bringing researchers from Ireland, Denmark
and Israel together to learn about cutting edge biology and form new collaborations.
Thus, the conference will be a showcase for the exciting and original research emanating
from these three small but innovative countries.