Impact of cerebrospinal fluid leukocyte infiltration and activated neuroimmune mediators on survival with HIV-associated cryptococcal meningitis.
<h4>Introduction</h4>Cryptococcal meningitis remains a prominent cause of death in persons with advanced HIV disease. CSF leukocyte infiltration predicts survival at 18 weeks; however, how CSF immune response relates to CSF leukocyte infiltration is unknown.<h4>Methods</h4>We...
Saved in:
| Main Authors: | , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2025-02-01
|
| Series: | PLoS Neglected Tropical Diseases |
| Online Access: | https://doi.org/10.1371/journal.pntd.0012873 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| Summary: | <h4>Introduction</h4>Cryptococcal meningitis remains a prominent cause of death in persons with advanced HIV disease. CSF leukocyte infiltration predicts survival at 18 weeks; however, how CSF immune response relates to CSF leukocyte infiltration is unknown.<h4>Methods</h4>We enrolled 401 adults with HIV-associated cryptococcal meningitis in Uganda who received amphotericin and fluconazole induction therapy. We assessed the association of CSF leukocytes, chemokine, and cytokine responses with 18-week survival.<h4>Results</h4>Participants with CSF leukocytes ≥50/microliter had a higher probability of 18-week survival compared with those with ≤50 cells/microliter (68% (52/77 vs. 52% (151/292); Hazard Ratio = 1.63, 95% confidence interval 1.14-2.23; p = 0.008). Survival was also associated with higher expression of T helper (Th)-1, Th17 cytokines, and immune regulatory elements. CSF levels of Programmed Death-1 Ligand, CXCL10, and Interleukin (IL)-2 independently predicted survival. In multivariate analysis, CSF leukocytes were inversely associated with CSF fungal burden and positively associated with CSF protein and immune parameters (interferon-gamma (IFN-γ), IL-17A, tumor necrosis factor alpha (TNF)-α, and circulating CD4+ and CD8+ T cells).<h4>Conclusion</h4>18-week survival after diagnosis of cryptococcal meningitis was associated with higher CSF leukocytes at baseline with greater T helper 1 (IFN-γ, IL-2 and TNF-α cytokines), T helper 17 (IL-17A cytokine) and CXCR3+ T cell (CXCL10 chemokine) responses. These results highlight the interdependent contribution of soluble and cellular immune responses in predicting survival and may support potential pathways for adjunctive immune therapy in HIV-associated cryptococcal meningitis. |
|---|---|
| ISSN: | 1935-2727 1935-2735 |