Mucosal and systemic antigen-specific antibody responses correlate with protection against active tuberculosis in nonhuman primates.
EBioMedicine
; 99: 104897, 2024 Jan.
Article
en En
| MEDLINE
| ID: mdl-38096687
ABSTRACT
BACKGROUND:
Increasing evidence supports that antibodies can protect against active tuberculosis (TB) but knowledge of potentially protective antigens, especially in the airways, is limited. The main objective of this study was to identify antigen-specific airway and systemic immunoglobulin isotype responses associated with the outcome of controlled latent Mycobacterium tuberculosis (Mtb) infection (LTBI) versus uncontrolled infection (TB) in nonhuman primates.METHODS:
In a case-control design, using non-parametric group comparisons with false discovery rate adjustments, we assessed antibodies in 57 cynomolgus macaques which, following low-dose airway Mtb infection, developed either LTBI or TB. We investigated airway and systemic IgG, IgA, and IgM responses in paired bronchoalveolar lavage and plasma samples prior to, two-, and 5-6-months post Mtb infection using an antigen-unbiased approach with Mtb glycan and proteome-wide microarrays.FINDINGS:
Macaques that developed LTBI (n = 36) had significantly increased airway and plasma IgA reactivities to specific arabinomannan (AM) motifs prior to Mtb infection compared to those that developed TB (n = 21; p < 0.01, q < 0.05). Furthermore, LTBI macaques had higher plasma IgG reactivity to protein MTB32A (Rv0125) early post Mtb infection (p < 0.05) and increasing airway IgG responses to some proteins over time.INTERPRETATION:
Our results support a protective role of pre-existing mucosal (lung) and systemic IgA to specific Mtb glycan motifs, suggesting that prior exposure to nontuberculous mycobacteria could be protective against TB. They further suggest that IgG to Mtb proteins early post infection could provide an additional protective mechanism. These findings could inform TB vaccine development strategies.FUNDING:
NIH/NIAID AI117927, AI146329, and AI127173 to JMA.Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Tuberculosis
/
Tuberculosis Latente
/
Mycobacterium tuberculosis
Límite:
Animals
Idioma:
En
Revista:
EBioMedicine
Año:
2024
Tipo del documento:
Article
País de afiliación:
Estados Unidos