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Isolating Central Nervous System Tissues and Associated Meninges for the Downstream Analysis of Immune cells

Isolating Central Nervous System Tissues and Associated Meninges for the Downstream Analysis of Immune cells

Published on: May 19, 2020

Cellular immune activation in cerebrospinal fluid from ugandans with cryptococcal meningitis and immune

David B Meya¹, Samuel Okurut², Godfrey Zziwa²

¹Infectious Disease Institute School of Medicine, College of Health Sciences Department of Medicine, Center for Infectious Diseases and Microbiology Translational Research, University of Minnesota, Minneapolis.

The Journal of Infectious Diseases

|December 11, 2014

Abstract

Background:

Human immunodeficiency virus (HIV)-associated cryptococcal meningitis (CM) is characterized by high fungal burden and limited leukocyte trafficking to cerebrospinal fluid (CSF). The immunopathogenesis of CM immune reconstitution inflammatory syndrome (IRIS) after initiation of antiretroviral therapy at the site of infection is poorly understood.

Methods:

We characterized the lineage and activation status of mononuclear cells in blood and CSF of HIV-infected patients with noncryptococcal meningitis (NCM) (n = 10), those with CM at day 0 (n = 40) or day 14 (n = 21) of antifungal therapy, and those with CM-IRIS (n = 10).

Results:

At diagnosis, highly activated CD8(+) T cells predominated in CSF in both CM and NCM. CM-IRIS was associated with an increasing frequency of CSF CD4(+) T cells (increased from 2.2% to 23%; P = .06), a shift in monocyte phenotype from classic to an intermediate/proinflammatory, and increased programmed death ligand 1 expression on natural killer cells (increased from 11.9% to 61.6%, P = .03). CSF cellular responses were distinct from responses in peripheral blood.

Conclusions:

After CM, T cells in CSF tend to evolve with the development of IRIS, with increasing proportions of activated CD4(+) T cells, migration of intermediate monocytes to the CSF, and declining fungal burden. These changes provide insight into IRIS pathogenesis and could be exploited to more effectively treat CM and prevent CM-IRIS.

Insights

Immune cells in the cerebrospinal fluid (CSF) change during HIV-associated cryptococcal meningitis (CM) and immune reconstitution inflammatory syndrome (IRIS). Understanding these changes in T cells and monocytes can help treat CM and prevent IRIS.

Area of Science:

Neuroimmunology
Infectious Diseases
Immunology

Background:

HIV-associated cryptococcal meningitis (CM) presents with high fungal load and low immune cell presence in cerebrospinal fluid (CSF).
The immune mechanisms driving CM immune reconstitution inflammatory syndrome (IRIS) after antiretroviral therapy are not well understood.

Purpose of the Study:

To investigate the cellular immune responses in the CSF of patients with HIV-associated meningitis.
To differentiate the immune profiles of cryptococcal meningitis (CM), non-cryptococcal meningitis (NCM), and CM-IRIS.

Main Methods:

Mononuclear cell lineage and activation were analyzed in blood and CSF.
Patients included those with NCM, CM at different treatment stages, and CM-IRIS.
Flow cytometry was used to assess T cell, monocyte, and natural killer cell phenotypes.

Main Results:

Both CM and NCM showed predominant CD8(+) T cells in CSF at diagnosis.
CM-IRIS was linked to increased CSF CD4(+) T cells, a shift to intermediate/proinflammatory monocytes, and higher PD-L1 on NK cells.
CSF immune cell profiles differed significantly from peripheral blood responses.

Conclusions:

CSF T cells evolve during CM, with increasing activated CD4(+) T cells and intermediate monocytes during IRIS development.
Declining fungal burden correlates with these immune shifts.
These findings offer insights into CM-IRIS pathogenesis and potential therapeutic targets.

Read full analysis

Keywords:

HIV cell activation cerebrospinal fluid cryptococcal meningitis cryptococcus immune responses

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