A new neutrophil type reshapes thinking about bovine tuberculosis
Aude Remot reports that cattle neutrophils include a regulatory subset, N reg, that behaves differently from conventional N conv during Mycobacterium bovis infection.
Bovine tuberculosis (bTB), caused by Mycobacterium bovis (Mb), is a chronic disease of cattle that also contributes to human tuberculosis cases. Despite its economic and public-health importance, some immune players in bTB have been overlooked. Aude Remot and colleagues recently described a previously unrecognized neutrophil subset in cattle and mice that looks a lot like conventional inflammatory neutrophils (N conv) but has a distinct identity. This subset, called regulatory neutrophils (N reg), carries MHC-II on its surface and can suppress lymphocyte proliferation, distinguishing it from N conv. In the study led by Aude Remot, researchers set out to compare how bovine N conv and N reg respond when exposed to a circulating virulent Mb strain from France and to the attenuated Mb BCG vaccine. By directly comparing these two neutrophil populations side by side during infection, the team aimed to reveal whether this cellular diversity matters for the way cattle control or respond to Mb, and whether it might affect our understanding of bTB pathophysiology and control strategies.
The study compared transcriptional profiles and activation of N conv and N reg during infection with Mb. The two neutrophil types displayed different transcriptional profiles and were differentially activated by Mb infection, showing that they do not respond identically to the same bacterium. Functionally, both N reg and N conv were able to efficiently kill Mb, demonstrating that each subset contributes to antimicrobial activity. However, N reg stood out by showing higher levels of phagocytosis activity and greater production of reactive oxygen species (ROS). N reg also exhibited higher mitochondrial activity and an ultrastructural organization that was different from that of N conv. These findings collectively describe distinct molecular and functional signatures for the two neutrophil subsets during exposure to both a virulent Mb strain and the attenuated Mb BCG vaccine.
These results provide the first functional characterization of bovine neutrophil subsets during Mb infection and reveal an added layer of complexity in the immune landscape of bTB. Recognizing that neutrophils are not a single uniform population but include regulatory cells with distinct transcriptional, metabolic and microbicidal properties may change how scientists interpret immune responses in infected cattle. For researchers and veterinarians, accounting for both N conv and N reg could influence the design and assessment of vaccines like Mb BCG vaccine, diagnostics, or treatments that aim to modulate host immunity. More broadly, this study urges the field to incorporate neutrophil diversity into models of bTB pathophysiology so that future efforts to manage this costly disease are informed by a fuller picture of the host response.
Understanding distinct neutrophil roles could improve how we evaluate vaccines and immune-based interventions against bTB. Taking neutrophil diversity into account may lead to better disease management and reduced economic losses in cattle.
Author: Maia Saint Vanne