Formal Comment on “Platelet-leucocyte interactions drive MMP-mediated tissue damage in tuberculosis” (Kirwan et al., 2026)
Year: 2026
Type: article
Abstract: We read with interest the article by Kirwan and colleagues, who demonstrate that platelet-leucocyte interactions via P-selectin/PSGL-1 drive matrix metalloproteinase (MMP)-mediated tissue damage in tuberculosis (TB) [1].The authors show that platelets infiltrate M.tb-infected tissues, form aggregates with monocytes and neutrophils, and promote secretion of MMP-1 and MMP-10, implicating the P-selectin/PSGL-1 axis as a host-directed therapeutic target.Although this pathway has not been directly tested in vivo, zebrafish models indicate that platelet inhibition enhances anti-mycobacterial immunity [2], and clinical data link low-dose aspirin to reduced stroke risk in tubercular meningitis [3], collectively supporting the broader rationale for anti-platelet interventions in TB.As clinicians managing patients with pulmonary TB, we recognize the translational potential of targeting the P-selectin/PSGL-1 axis.However, we wish to raise several methodological and clinical considerations that may merit further discussion.First, the exclusive use of platelets and monocytes from healthy volunteers for in vitro co-culture experiments may not fully capture the pathophysiology in TB patients.The authors demonstrate that platelets enhance MMP-1 and MMP-10 secretion from M.tb-infected monocytes, with effects mediated in part through P-selectin/PSGL-1 interactions.However, these experiments used cells from healthy donors with no known TB exposure [1].In TB patients, chronic inflammatory exposure may precondition both platelets and monocytes, potentially altering their activation status, receptor expression profiles, and functional responses.Notably, the authors themselves observe that platelet aggregation responses to ADP are significantly reduced in TB patients compared to healthy controls (Fig 4a) [1], yet the mechanistic experiments used platelets from healthy donors with presumably normal aggregation capacity.It remains possible, therefore, that the observed P-selectin/PSGL-1-dependent effects may differ quantitatively or qualitatively in cells from TB patients.Future studies replicating key experiments using cells isolated from TB patients would help validate the mechanistic pathway in the relevant pathological context.Second, the optimal timing of antiplatelet intervention during TB treatment warrants further consideration.The authors report that platelet aggregation in TB patients is reduced at diagnosis and continues to decline during the first two weeks of anti-TB
Source: PLoS Pathogens
Author: Qingqing Shan
Language: English
Subfield: Infectious Diseases
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,043
OpenAlex ID: W7214147434