AUTHOR=Bchiri Soumaya , Bahrini Khadija , Teles Rosane M. B. , Alaya Ameni Ben , Kamel Houssem Eddine , West Julie , Rategh Kimia , Bouzekri Asma , Bousalem Eya , Ouni Rim , Fassatoui Meriem , Mardassi Helmi , Dekhil Neira , Belghith Issam Ben , Lahiani Rym , Romdhane Emna , Ben-Ali Meriem , Rammeh Soumaya , Ferjani Asma , Ben-Saleh Mamia , Barbouche Mohamed-Ridha , Modlin Robert L. , Benabdessalem Chaouki 
  
TITLE=Interleukin-15 correlates with cytotoxic immune networks in cervical tuberculous lymphadenitis
  
JOURNAL=Frontiers in Immunology
  
VOLUME=Volume 17 - 2026
  
YEAR=2026
  
URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2026.1831890
  
DOI=10.3389/fimmu.2026.1831890
  
ISSN=1664-3224
  
ABSTRACT=IntroductionCervical tuberculous lymphadenitis (CTL) represents a localized manifestation of Mycobacterium tuberculosis infection in which immune responses are organized within lymphoid tissue. While cytotoxic lymphocyte responses contribute to antimycobacterial immunity, the cytokine networks coordinating these responses in human lymph node tuberculosis remain incompletely defined.MethodsWe performed integrated immune profiling of patients with CTL (n = 60) and non-tuberculous cervical lymphadenopathy (CNTL; n = 44). Immune−gene expression was quantified in peripheral blood and lymph node mononuclear cells by qPCR. Systems-level analyses including principal component and correlation-network approaches were used to define coordinated immune pathways. Serum IL−15 was measured by ELISA, and tissue localization of IL−15 and IL−15Rα was examined by immunohistochemistry.ResultsCTL was characterized by a structured cytotoxic immune program enriched for granulysin, granzyme B, perforin, IFN-γ, and CCL5. Network analysis identified IL-15 as a highly connected hub within this cytotoxic module in CTL. IL-15 transcripts were significantly elevated in both blood and lymph node compartments (p = 0.0003; p = 0.0007, respectively) and strongly correlated with cytotoxic effector genes. Circulating IL-15 concentrations were higher in CTL than CNTL (p < 0.0001) and increased with GeneXpert-defined bacillary burden (AUC 0.73). Immunohistochemistry demonstrated IL-15 and IL-15Rα expression within CD68+ macrophages localized to granulomatous regions, consistent with macrophage-mediated IL-15 trans-presentation within sites of infection.ConclusionsThese findings identify IL−15 as a potential central organizer of cytotoxic immune pathways in CTL and highlight IL−15–linked immune signatures as biologically informative features of CTL immunopathogenesis.