---
title: "PD‑1/PD‑L1 Blockade Worsens Chronic Nocardia brasiliensis Actinomycetoma in BALB/c Mice"
id: "pubmed-42770687"
canonical_url: "https://medichelpline.com/clinical-feed/pubmed-42770687"
content_type: "clinical_feed_article"
specialty: "Critical Care"
source_name: "PubMed / NCBI"
source_url: "https://pubmed.ncbi.nlm.nih.gov/42770687/"
doi: "10.1080/08820139.2026.2731121"
published_at: "2026-09-22T00:00:00.000Z"
evidence_level: "Journal Article"
license: "CC-BY-NC-4.0 / Informational Use"
---
# PD‑1/PD‑L1 Blockade Worsens Chronic Nocardia brasiliensis Actinomycetoma in BALB/c Mice
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/pubmed-42770687
- **Specialty:** [Critical Care](https://medichelpline.com/clinical-feed/critical-care.md)
- **Primary Source:** PubMed / NCBI
- **Source URL:** [Original Journal Publication](https://pubmed.ncbi.nlm.nih.gov/42770687/)
- **DOI:** [10.1080/08820139.2026.2731121](https://doi.org/10.1080%2F08820139.2026.2731121)
- **Published At:** 2026-09-22T00:00:00.000Z
- **Evidence Rating:** Journal Article
## Executive GIST (TL;DR)
- Background: Checkpoint blockade targeting **PD-1/PD-L1** restores exhausted T cells in cancer but may reactivate latent or chronic infections; its role in granulomatous infectious diseases is poorly understood. - Model and intervention: BALB/c mice with established chronic **Nocardia brasiliensis** actinomycetoma were treated with the **PD-L1 inhibitor atezolizumab** to evaluate effects on infection containment and immune responses. - Local lesion findings: Actinomycetoma lesions showed a sparse lymphocytic infiltrate; remaining **CD8+ T cells** within lesions expressed high levels of PD-1. - Key clinical/pathologic outcomes: Anti–PD-L1 treatment was associated with increased mortality, disruption of **granuloma** integrity, worsened necrosis, and higher bacterial loads among survivors. - Systemic signs and cytokines: Death was not directly attributed in the study; there were no classic clinical signs of sepsis and no elevations in hallmark proinflammatory cytokines such as **IL-6** and **TNF-α**. Instead, PD-L1 blockade produced a paradoxical cytokine pattern with elevated **IL-12p70** and **IL-10**. - Immune microenvironment: Despite checkpoint blockade, the neutrophil-dominant lesion microenvironment was not reprogrammed toward effective bacterial clearance. - Methodological limitation: The study lacked an isotype control, which authors acknowledge as a limitation. - Conclusion and implication: In this murine model, intact **PD-1/PD-L1** signaling appears to help maintain immune balance and bacterial containment; blocking this axis led to severe immunopathology and reduced survival, indicating potential risks when applying checkpoint inhibitors in the setting of chronic infections.
## Clinical Analysis & Structured Key Points
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Online ahead of print. # Blockade of the PD-1 / PD-L1 Axis Exacerbates Chronic _Nocardia Brasiliensis_ Infection by Disrupting Bacterial Immune Containment in BALB/c Mice [Maria L Ruiz-de la Cruz](https://pubmed.ncbi.nlm.nih.gov/?term=Ruiz-de+la+Cruz+ML&cauthor_id=42770687)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42770687/#full-view-affiliation-1 "Department of Immunology, School of Medicine and Dr. Jose Eleuterio Gonzalez University Hospital, Universidad Autonoma de Nuevo León, Monterrey, Mexico."), [Anna V Vazquez-Marmolejo](https://pubmed.ncbi.nlm.nih.gov/?term=Vazquez-Marmolejo+AV&cauthor_id=42770687)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42770687/#full-view-affiliation-1 "Department of Immunology, School of Medicine and Dr. Jose Eleuterio Gonzalez University Hospital, Universidad Autonoma de Nuevo León, Monterrey, Mexico."), [Manuel G Mejia-Torres](https://pubmed.ncbi.nlm.nih.gov/?term=Mejia-Torres+MG&cauthor_id=42770687)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42770687/#full-view-affiliation-1 "Department of Immunology, School of Medicine and Dr. Jose Eleuterio Gonzalez University Hospital, Universidad Autonoma de Nuevo León, Monterrey, Mexico."), [Maria A Castro-Corona](https://pubmed.ncbi.nlm.nih.gov/?term=Castro-Corona+MA&cauthor_id=42770687)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42770687/#full-view-affiliation-1 "Department of Immunology, School of Medicine and Dr. Jose Eleuterio Gonzalez University Hospital, Universidad Autonoma de Nuevo León, Monterrey, Mexico."), [Mario C Salinas-Carmona](https://pubmed.ncbi.nlm.nih.gov/?term=Salinas-Carmona+MC&cauthor_id=42770687)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42770687/#full-view-affiliation-1 "Department of Immunology, School of Medicine and Dr. Jose Eleuterio Gonzalez University Hospital, Universidad Autonoma de Nuevo León, Monterrey, Mexico.") Affiliations Expand ### Affiliation * 1 Department of Immunology, School of Medicine and Dr. Jose Eleuterio Gonzalez University Hospital, Universidad Autonoma de Nuevo León, Monterrey, Mexico. * PMID: **42770687** * DOI: [ 10.1080/08820139.2026.2731121 ](https://doi.org/10.1080/08820139.2026.2731121) Item in Clipboard # Blockade of the PD-1 / PD-L1 Axis Exacerbates Chronic _Nocardia Brasiliensis_ Infection by Disrupting Bacterial Immune Containment in BALB/c Mice Maria L Ruiz-de la Cruz et al. Immunol Invest. 2026. Show details Display options Display options Format Abstract PubMed PMID Immunol Invest Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Immunol+Invest%22%5Bjour%5D&sort=date&sort_order=desc) * [ Search in NLM Catalog ](https://www.ncbi.nlm.nih.gov/nlmcatalog?term=%22Immunol+Invest%22%5BTitle+Abbreviation%5D) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42770687/) . 2026 Sep 22:1-27. doi: 10.1080/08820139.2026.2731121. Online ahead of print. ### Authors [Maria L Ruiz-de la Cruz](https://pubmed.ncbi.nlm.nih.gov/?term=Ruiz-de+la+Cruz+ML&cauthor_id=42770687)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42770687/#short-view-affiliation-1 "Department of Immunology, School of Medicine and Dr. Jose Eleuterio Gonzalez University Hospital, Universidad Autonoma de Nuevo León, Monterrey, Mexico."), [Anna V Vazquez-Marmolejo](https://pubmed.ncbi.nlm.nih.gov/?term=Vazquez-Marmolejo+AV&cauthor_id=42770687)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42770687/#short-view-affiliation-1 "Department of Immunology, School of Medicine and Dr. Jose Eleuterio Gonzalez University Hospital, Universidad Autonoma de Nuevo León, Monterrey, Mexico."), [Manuel G Mejia-Torres](https://pubmed.ncbi.nlm.nih.gov/?term=Mejia-Torres+MG&cauthor_id=42770687)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42770687/#short-view-affiliation-1 "Department of Immunology, School of Medicine and Dr. Jose Eleuterio Gonzalez University Hospital, Universidad Autonoma de Nuevo León, Monterrey, Mexico."), [Maria A Castro-Corona](https://pubmed.ncbi.nlm.nih.gov/?term=Castro-Corona+MA&cauthor_id=42770687)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42770687/#short-view-affiliation-1 "Department of Immunology, School of Medicine and Dr. Jose Eleuterio Gonzalez University Hospital, Universidad Autonoma de Nuevo León, Monterrey, Mexico."), [Mario C Salinas-Carmona](https://pubmed.ncbi.nlm.nih.gov/?term=Salinas-Carmona+MC&cauthor_id=42770687)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42770687/#short-view-affiliation-1 "Department of Immunology, School of Medicine and Dr. Jose Eleuterio Gonzalez University Hospital, Universidad Autonoma de Nuevo León, Monterrey, Mexico.") ### Affiliation * 1 Department of Immunology, School of Medicine and Dr. Jose Eleuterio Gonzalez University Hospital, Universidad Autonoma de Nuevo León, Monterrey, Mexico. * PMID: **42770687** * DOI: [ 10.1080/08820139.2026.2731121 ](https://doi.org/10.1080/08820139.2026.2731121) Item in Clipboard Cite Display options Display options Format Abstract PubMed PMID ## Abstract **Background:** Therapeutic blockade of the PD-1/PD-L1 axis is a key strategy in cancer immunotherapy to reverse T cell exhaustion. However, this approach carries the risk of reactivating latent pathogens in individuals with chronic infections. The role of this immune checkpoint in granulomatous infectious diseases, particularly chronic actinomycetoma, remains largely unexplored. **Methods:** To investigate this, we treated BALB/c mice with established chronic _Nocardia brasiliensis_ actinomycetoma using the PD-L1 inhibitor atezolizumab. We assessed survival, clinical progression, and histopathology, and characterized systemic versus local immune responses through cytokine analysis and flow cytometry of lymphoid organs and lesion tissue. **Results:** Actinomycetoma lesions had a paucicellular lymphocyte infiltrate, yet the few CD8+ T cells present exhibited high PD-1 expression. Atezolizumab treatment was associated with increased mortality, loss of granuloma integrity, exacerbated necrosis, and higher bacterial load in survivors, although the precise cause of death was not directly established. These outcomes occurred despite the absence of classical clinical signs of sepsis and elevations in hallmark proinflammatory cytokines such as interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α). PD-L1 blockade triggered a paradoxical cytokine profile (elevated IL-12p70 and IL-10) but failed to reprogram the neutrophil-dominated microenvironment. **Conclusion:** These findings provide evidence that PD-1/PD-L1 signaling is associated with the maintenance of immune equilibrium and bacterial containment in chronic _N. brasiliensis_ infection in our murine model. Although the absence of an isotype control remains a methodological limitation, anti-PD-L1 therapy was accompanied by severe immunopathology and reduced survival, highlighting potential risks of checkpoint inhibitors during underlying chronic infections. **Keywords:** Actinomycetoma; PD-1/PD-L1 axis; chronic infection; immune checkpoint inhibitor; immune dysregulation. [PubMed Disclaimer](https://pubmed.ncbi.nlm.nih.gov/disclaimer/) ## Similar articles * [ Depression decreases immunity and PD-L1 inhibitor efficacy via the hypothalamic-pituitary-adrenal (HPA) axis in triple-negative breast cancer. ](https://pubmed.ncbi.nlm.nih.gov/39579799/) Yu S, Gan C, Li W, Zhang Q, Cai Y, Xu J, Huang R, Yao S, Cheng L, Cheng H.Yu S, et al.Biochim Biophys Acta Mol Basis Dis. 2025 Feb;1871(2):167581. doi: 10.1016/j.bbadis.2024.167581. Epub 2024 Nov 22.Biochim Biophys Acta Mol Basis Dis. 2025.PMID: 39579799 * [ Increased expression of the PD-1/PD-L1 regulatory axis in tissue leukocytes from experimental actinomycetoma by Nocardia brasiliensis in BALB/c mice. ](https://pubmed.ncbi.nlm.nih.gov/40368069/) Vázquez-Marmolejo AV, Duarte-Mata DI, Ruiz-De La Cruz ML, López-López N, Salinas-Carmona MC, Mejía-Torres M.Vázquez-Marmolejo AV, et al.Microb Pathog. 2025 Aug;205:107697. doi: 10.1016/j.micpath.2025.107697. 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