Fever temperatures increase immune cell metabolism, proliferation and activity, but they also—in a particular subset of T cells—induce mitochondrial stress and DNA damage followed by cell death, scientists from the Vanderbilt University Medical Center found.
Its conclusion, published in the Science Immunology, provides a cell-based understanding of heat shock and may help elucidate the underlying mechanism through which persistent inflammation results in cancer development.
Although how fever temperatures specifically affect cells has not been researched extensively, said Jeff Rathmell, Ph.D., Cornelius Vanderbilt Professor of Immunobiology and the corresponding author of the new study. The majority of studied temperature effects are associated with agriculture and its consequences for bread and livestock, as Klimenko mentioned.
It’s challenging to change the temperature of animal models without causing stress, and cells in the laboratory are generally cultured in incubators that are set at human body temperature: It rises to; 37DC or 98.6 F.
It is 37.0ºC, he notes, not a figure reflective of most inflammatory reactions; few, Rathmell adds, who also directs the Vanderbilt Center for Immunobiology, have really tried to find out what occurs when temperature is altered.
Here the researchers found out that not all Th1 cells die instead the cells switch their type, change their mitochondria and become more stress-resistant. “Then there’s a wave of stress, some of the cells die, but the ones that do well, the ones that are better—they grow even more and make even more cytokine (immune signalling molecules),” Rathmell said.
Thus, Heintzman was successfully allowed to define the molecular process of the cell response at fever temperatures. He discovered that heat quickly inactivated electron transport chain complex 1 (ETC1) , a mitochondrial enzyme responsible for production of ATP. ETC1 impairment engages signals that appear to induce DNA damage and the p53 protein that is helpful in DNA repair or cell death to avoid genomic instability. Th1 cells were found to be more receptive than other T cell subsets to damaged ETC1.
The research has shown that heat can be mutagenic if cells which respond to chemicals signalling from mitochondria do not fix the damage to DNA or die.
‘If tissue temperatures are raised for extended periods of time,’ Heintzman said, chronic inflammation could be how some cells become tumorigenic, adding that up to a quarter of all cancers are associated with chronic inflammation.
Reference:
Darren Heintzman et al, Subset-specific mitochondrial stress and DNA damage shape T cell responses to fever and inflammation, Science Immunology (2024). DOI: 10.1126/sciimmunol.adp3475.
