{
  "abstract": "Background\n\nPneumocystis pneumonia (PCP) is a severe fungal infection that predominantly affects individuals with compromised immune systems, specifically those with adaptive immunodeficiency. The mechanisms governing the remodeling of the innate immune system in the context of PCP, particularly in the presence of complete adaptive immunodeficiency, remain insufficiently elucidated. Here, using single-cell RNA sequencing (scRNA-seq) in a murine PCP model, we reveal how innate immune responses are remodeled in the absence of adaptive immunity, providing new mechanistic insights into PCP pathogenesis and a foundation for targeted therapy.Methods\n\nAn experimental model of PCP was established using male CB-17 SCID mice with adaptive immunodeficiency. Mice were weight-matched into six pairs and randomly divided into a PCP group and a control (CON) group (n = 6 per group) using a computer-generated random sequence; PCP mice received an intranasal instillation of 1 × 10⁶ cysts in 100 μL sterile phosphate-buffered saline (PBS) under isoflurane anesthesia, whereas CON mice received an equal volume of sterile PBS alone. Lung tissues were collected for scRNA-seq to profile pulmonary innate immune cells. Bioinformatic analyses were employed to characterize several subsets of monocyte-derived macrophages, and immunofluorescence and quantitative reverse transcription PCR were used to validate these findings.Results\n\nscRNA-seq indicated an expansion of Ccr2 ⁺ monocyte-derived Nckap5 ⁺ macrophages in PCP mice, which was associated with anti-inflammatory features and activation of pro-proliferative pathways. Inhibition of the MAPK pathway using Adezmapimod effectively reversed the induction of Nckap5 (4.463 ± 0.125 vs. 0.991 ± 0.052, P < 0.001) and the expression of anti-inflammatory cytokines, including Il10 (44.090 ± 1.246 vs. 4.131 ± 0.151, P < 0.001), Arg1 (2.455 ± 0.135 vs. 0.918 ± 0.018, P < 0.001) and Tgf β (1.147 ± 0.043 vs. 0.994 ± 0.031, P < 0.01).Conclusion\n\nThis study advances understanding of PCP pathogenesis and identifies Nckap5 ⁺ macrophages as a potential therapeutic target for patients with compromised immune systems.",
  "abstract_shown": true,
  "affiliations": [
    "Medical Research Center, Beijing Institute of Respiratory Medicine and Beijing Chao-Yang Hospital, Capital Medical University, Beijing 100020, China.",
    "Laboratory for Clinical Medicine, Capital Medical University, Beijing 100020, China.",
    "Department of Respiratory and Critical Care Medicine, Beijing Institute of Respiratory Medicine and Beijing Chao-Yang Hospital, Capital Medical University, Beijing 100020, China."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 7,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Lin Gu"
    },
    {
      "affs": [
        0
      ],
      "name": "Wan Peng"
    },
    {
      "affs": [
        2
      ],
      "name": "Hanyujie Kang"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Yuling Xu"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Jieqiong Li"
    },
    {
      "affs": [
        1,
        2
      ],
      "name": "Zhaohui Tong"
    },
    {
      "affs": [
        1,
        2
      ],
      "name": "Nan Song"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/3eaxdv751h59q.bib",
  "cited_by": 1,
  "doi": "10.1097/id9.0000000000000216",
  "fulltext_url": "https://europepmc.org/articles/PMC13682803",
  "id": "3eaxdv751h59q",
  "issns": [
    "2096-9511",
    "2693-8839"
  ],
  "landing_url": "https://europepmc.org/article/MED/42904279",
  "language": "eng",
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2713|Pneumocystis jirovecii pneumonia detection and treatment"
    ]
  ],
  "openalex": "W7164065985",
  "pdf_url": "https://europepmc.org/articles/PMC13682803?pdf=render",
  "pmcid": "PMC13682803",
  "pmid": "42904279",
  "published": "2026-06-09",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/3eaxdv751h59q.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:59Z",
      "native_id": "MED:42904279",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42904279"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2713|Pneumocystis jirovecii pneumonia detection and treatment",
      "subfield": "epidemiology-public-health"
    }
  ],
  "title": "Pulmonary innate immune remodeling in Pneumocystis pneumonia with adaptive immunodeficiency.",
  "title_text": "Pulmonary innate immune remodeling in Pneumocystis pneumonia with adaptive immunodeficiency.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:19:59Z",
  "url": "https://research.draconitic.com/paper/3eaxdv751h59q",
  "venue": "Infectious diseases & immunity",
  "versions": []
}