Protein maps trace how liver, lung and spleen respond to disseminated Talaromyces marneffei infection

Disseminated infection with the pathogenic fungus Talaromyces marneffei can spread through several organs at once, yet most molecular studies of the host response have examined one tissue at a time. A new study published in iMetaMed by researchers at Guangxi Medical University changes that perspective, offering an organ-resolved view of how the liver, lung and spleen respond in an immunosuppressed mouse model of infection.

The team assessed fungal burden and tissue pathology seven days after infection using colony-forming unit assays together with H&E and PAS staining. Liver, lung and spleen samples from infected and control mice then underwent LC-MS/MS-based profiling of the global proteome as well as four post-translational modification layers: the acetylome, lactylome, phosphoproteome and ubiquitinome.

Across all three organs, infection was associated with acute-phase proteins and immune pathways, together with marked changes in glucose, amino acid and lipid metabolism. But the shared response was only part of the picture. The liver, lung and spleen also displayed distinct protein-abundance and modification patterns, indicating that a disseminated pathogen encounters different host regulatory environments as it spreads through the body.

Each organ carried its own molecular signature. The liver showed especially prominent ubiquitination-related changes that accompanied shifts in protein abundance, whereas the spleen had the broadest set of differential acetylation sites. Lactylation-associated signals and several histone modifications were most marked in the liver. The authors note an important limitation: because the work used whole-organ homogenates, these patterns could reflect changes within individual cells, differences in cellular composition between tissues, or both.

At the level of individual lysine positions, the overlap among ubiquitination, acetylation and lactylation was limited. Yet functional analysis repeatedly pointed to related pathways, particularly metabolic pathways and immune signaling. This pattern suggests that distinct modification systems may contribute to a common host response through different molecular sites, rather than through a single uniform molecular switch.

The researchers also used the phosphoproteomic data to infer kinase-associated signatures computationally. The predicted patterns differed by organ, so the analysis was used to prioritize hypotheses rather than to claim directly measured kinase activity. Mapping these signatures onto known drug-target relationships produced candidate compounds for exploratory testing, and pitavastatin was additionally selected as a metabolism-informed candidate.

In an exploratory in vivo experiment, pitavastatin significantly reduced fungal burden in the liver. Changes in lung and spleen burden did not reach statistical significance, although pitavastatin-treated mice showed improved survival relative to vehicle controls. The experiment did not include a standard antifungal comparator, so the findings do not establish clinical benefit, a replacement for antifungal treatment, or the mechanism responsible for the observed effects.

By bringing protein abundance and four modification layers together across organs, the study provides a resource for investigating host-pathogen interactions in disseminated talaromycosis. The authors note that the analysis captures a single time point and that its kinase predictions require direct biochemical validation. Future work can use the map to test cell-type-specific mechanisms and clarify whether the highlighted pathways can support host-directed therapeutic strategies.

The study, published on 21 October 2026 under DOI 10.1002/imm3.70069, was released by the International Society for Health Data Science as a peer-reviewed publication, with the authors declaring no competing interests.

Subject of Research: Multi-organ proteomic and post-translational modification profiling of host responses to Talaromyces marneffei infection in mice

Article Title: Multi-organ protein maps reveal shared and organ-specific host responses to Talaromyces marneffei infection

Article References: Multi-organ protein maps reveal shared and organ-specific host responses to Talaromyces marneffei infection. Original publication (Bibliographic details unavailable.)

Image Credits: AI Generated

DOI: Not provided

Keywords: Talaromyces marneffei, talaromycosis, proteomics, acetylome, lactylome, phosphoproteome, ubiquitinome, liver, spleen, pitavastatin, host-pathogen interactions, mouse model