The Forum: Spring 2008

Spring 2008 journal of the Honors Program at the University of North Dakota. The issue includes stories, poems, essays and art by undergraduate students.https://commons.und.edu/und-books/1061/thumbnail.jp

The Forum: Fall 2007

Fall 2007 journal of the Honors Program at the University of North Dakota. The issue includes stories, poems, essays and art by undergraduate students.https://commons.und.edu/und-books/1040/thumbnail.jp

The Forum: Spring 2010

Spring 2010 journal of the Honors Program at the University of North Dakota. The issue includes stories, poems, essays and art by undergraduate students.https://commons.und.edu/und-books/1063/thumbnail.jp

Intracellular growth of Mycobacterium tuberculosis after macrophage cell death leads to serial killing of host cells

A hallmark of pulmonary tuberculosis is the formation of macrophage-rich granulomas. These may restrict Mycobacterium tuberculosis (Mtb) growth, or progress to central necrosis and cavitation, facilitating pathogen growth. To determine factors leading to Mtb proliferation and host cell death, we used live cell imaging to track Mtb infection outcomes in individual primary human macrophages. Internalization of Mtb aggregates caused macrophage death, and phagocytosis of large aggregates was more cytotoxic than multiple small aggregates containing similar numbers of bacilli. Macrophage death did not result in clearance of Mtb. Rather, it led to accelerated intracellular Mtb growth regardless of prior activation or macrophage type. In contrast, bacillary replication was controlled in live phagocytes. Mtb grew as a clump in dead cells, and macrophages which internalized dead infected cells were very likely to die themselves, leading to a cell death cascade. This demonstrates how pathogen virulence can be achieved through numbers and aggregation states. DOI: http://dx.doi.org/10.7554/eLife.22028.00