A little fat won’t kill you – well, this may be a lie, but could I interest you in a story where a little fat could ‘save’ you after infection? This discovery definitely got my motor running. Could the adipocyte (a fat cell) act as an immune cell and clear the infection? Unfortunately, Caputa et al. answered that question with a no. However, they did find out that with a little help, adipocytes are not as defenceless as we thought them to be in the fight against bacterial pathogens.
First, let me introduce you to my party people in the club: white, brown and beige adipose tissue. White and brown are most commonly known, with the main difference being in the lipid content (very high in a single big droplet for white whereas high with multiple smaller lipid droplets for brown), mitochondria amount (high in brown leading to the color from iron in mitochondria), energy (white stores energy, brown generates energy- remember mitochondria is the powerhouse of the cell), and localization (white is usually found beneath the skin and in the abdomen, while brown isstored around shoulder, neck, kidneys, and spinal cord). Beige adipose tissues arise from white using appropriate stimuli.
In the article we are focusing on today, Caputa et al. found out what happens with adipose tissue associated with lymphoid tissue, so called perinodal adipose tissue (PAT), following the subcutaneous bacterial infection of Listeria monocytogenes (Lm). PAT has unique characteristics of both white and brown adipose tissues.
To confirm whether PAT could help cytotoxic T cell expansion, Caputa et al. used mice lacking mature adipocytes and mice lacking lipase (enzyme that breaks down fat) that has the ability to liberate the free fatty acids. Compared to normal mice there was no difference in T cell number, T cell activation and bacterial number in response to a loss of PAT or lipase. So adipocytes were not a necessity for developing a protective immune response against Lm infection.
Amongst other cells, Lm can infect PAT adipocytes as well. Interestingly, PAT adipocytes are able to clear the infection within themselves, by themselves. Well, almost by themselves. NK cells and iNKT cells (invariant NK T cells) within PAT were providing the adipocytes with IFN-gamma that redirects adipocytes’ function from metabolism to host defence. The researchers used antibodies to block NK and iNKT cells and PAT adipocytes were unable to refocus their function and fail to clear out the infection. Furthermore, IFN-gamma stimulation induced the expression of NOD1 (an intracellular pathogen recognition receptor) that synergizes with IFN-gamma and leads to high generation of iNOS (protein that generates Nitric Oxide (NO) from arginine). NO, on the other hand, is bactericidal and can diffuse across membranes.
This discovery is most interesting in terms of finding out that adipocytes can do much more than just provide us with homeostasis benefits. Several other pathogens have been reported to home in the adipose tissues, such as HIV, Trypanosoma cruzi, Mycobacterium canettii and Coxiella burnetii. It would be interesting to find out if and which immune evasion systems these pathogens use in adipose tissues? The next question is whether such discoveries could lead us to a better understanding of the mentioned pathogens? We will keep you updated whenever these are answered, at Antibuddies!
Caputa G, Matsushita M, Sanin DE, Kabat AM, Edwards-Hicks J, Grzes KM, Pohlmeyer R, Stanczak MA, Castoldi A, Cupovic J, Forde AJ, Apostolova P, Seidl M, van Teijlingen Bakker N, Villa M, Baixauli F, Quintana A, Hackl A, Flachsmann L, Hässler F, Curtis JD, Patterson AE, Henneke P, Pearce EL, Pearce EJ. Intracellular infection and immune system cues rewire adipocytes to acquire immune function. Cell Metab. 2022 May 3;34(5):747-760.e6. doi: 10.1016/j.cmet.2022.04.008.
Article author: Ines Poljak. Ines is a MSc graduate from University of Copenhangen who worked on multiple myeloma bone disease. She worked in several clinical laboratories before committing herself completely to research.