Finding. The lung cells that kill Cryptococcus neoformans do not fire up mitochondria. They go glycolytic and put mitochondrial enzymes down. Nair, Luitel and Wozniak show that J774A.1 macrophages exposed to the fungus raise GLUT-1, hexokinase, HIF-1α and lactate, and lower ATP5a and IDH2. G6PD, ACAC, ASS1 and PRDX2 fall with them. Inhibit the pentose-phosphate pathway, and G6PD falls further while intracellular fungal burden drops. In the infected lung the same GLUT-1 and hexokinase rise appears in antifungal Ly6c-minus monocyte-like macrophages, not in CD11b-positive dendritic cells that permit fungal growth, even though both subsets phagocytose equally.
Why this paper matters
Equal uptake, unequal metabolism, unequal killing. That is a cleaner sentence than "macrophages need glycolysis." The mitochondrial content is the down-shift: ATP synthase and IDH2 are not the antifungal engine here. If you model host-directed therapy against Cryptococcus, a mitochondrial booster might be the wrong knob and a PPP or glycolytic lever the right one, at least in this subset.
The in vivo split is the part to steal. Prior work from the group already pointed at glycolysis in antifungal cells. This preprint adds the mitochondrial decrement and a DC that refuses the program.
What they actually measured
Ten pathways, flow markers, inhibitors, killing assays, and a pulmonary infection. Female Ly6c- macrophages are the in vivo glycolytic subset named in the abstract. Other markers are described as limited or subset-specific in vivo, so do not invent a full matching omics atlas in the lung.
How to read the score
Low 80s. Mitochondrial enzymes down, glycolysis up, subset specificity. Confidence is medium: markers, not Seahorse, and PPP inhibition could have fungal-side effects.
Caveats
J774A.1 is a cell line. ATP5a is not a coupling assay. Sex is specified for the in vivo GLUT-1/HK result. Do not treat PPP inhibitors as antifungals from this brief.
What to do with it
If you profile lung phagocytes after Cryptococcus, gate GLUT-1/HK on Ly6c- macrophages versus DCs and add ATP5a. If you screen host metabolism drugs, include a PPP arm and a DC-versus-macrophage split. Do not conclude that mitochondria are irrelevant to antifungal immunity; conclude that this antifungal subset is not using them as the primary kill switch.