A roadmap for navigating partner engagement in community-based autopsy studies: Lessons from the field in rural KwaZulu-Natal, South Africa.

Background: The measurement of cause-specific mortality is critical for health system planning but remains a challenge in many low-resource settings due to societal, legal, and logistical barriers. We present a co-development process with community members for the design and implementation of an autopsy program to improve cause of death data in a historically underserved population.

Methods: We sought to develop an autopsy program at the Africa Health Research Institute (AHRI) Health and Demographic Surveillance Site (HDSS).

Detection of in human tissue via RNA hybridization.

Rationale: Accurate TB diagnosis is hampered by the variable efficacy of the widely-used Ziehl-Neelsen (ZN) staining method to identify ( ) acid-fast bacilli (AFB). Here, we sought to circumvent this current limitation through direct detection of mRNA.

Objectives: To employ RNAscope to determine the spatial distribution of mRNA within tuberculous human tissue, to appraise ZN-negative tissue from confirmed TB patients, and to provide proof-of-concept of RNAscope as a platform to inform TB diagnosis and biology.

Tissue-resident-like CD4+ T cells secreting IL-17 control Mycobacterium tuberculosis in the human lung.

T cell immunity is essential for the control of tuberculosis (TB), an important disease of the lung, and is generally studied in humans using peripheral blood cells. Mounting evidence, however, indicates that tissue-resident memory T cells (Trms) are superior at controlling many pathogens, including Mycobacterium tuberculosis (M. tuberculosis), and can be quite different from those in circulation.

Differential skewing of donor-unrestricted and γδ T cell repertoires in tuberculosis-infected human lungs.

Unconventional T cells that recognize mycobacterial antigens are of great interest as potential vaccine targets against tuberculosis (TB). This includes donor-unrestricted T cells (DURTs), such as mucosa-associated invariant T cells (MAITs), CD1-restricted T cells, and γδ T cells. We exploited the distinctive nature of DURTs and γδ T cell receptors (TCRs) to investigate the involvement of these T cells during TB in the human lung by global TCR sequencing.

induces decelerated bioenergetic metabolism in human macrophages.

How () rewires macrophage energy metabolism to facilitate survival is poorly characterized. Here, we used extracellular flux analysis to simultaneously measure the rates of glycolysis and respiration in real time. infection induced a quiescent energy phenotype in human monocyte-derived macrophages and decelerated flux through glycolysis and the TCA cycle.

Heme oxygenase-1 promotes granuloma development and protects against dissemination of mycobacteria.

Non-tuberculous mycobacterial (NTM) infections occur in both immunocompromised and immunocompetent hosts and are an increasingly recognized cause of morbidity and mortality. The hallmark of pulmonary mycobacterial infections is the formation of granuloma in the lung. Our study focuses on the role of heme oxygenase-1 (HO-1), a cytoprotective enzyme, in the regulation of granuloma development and maturation following infection with Mycobacterium avium.