Immunopathological signatures in congenital tuberculosis-a case-matched study

Area of Science:

• Immunology
• Neonatal Medicine
• Infectious Diseases

Background:

• Congenital tuberculosis (CTB) is a rare but severe condition with high mortality in neonates.
• The immune cell characteristics in CTB neonates are not well understood.
• Existing data on adult tuberculosis (ATB) provides a limited comparison.

Purpose of the Study:

• To characterize the immune cell profiles in neonates with congenital tuberculosis.
• To investigate the functional and phenotypic changes in immune cells during CTB.
• To explore potential immune mechanisms contributing to CTB mortality.

Main Methods:

• A case-control study comparing nine CTB neonates with nine paired healthy control (pHC) neonates.
• Analysis included routine blood tests, C-reactive protein (CRP) levels, and lymphocyte subset profiling via flow cytometry.
• Exploratory single-cell RNA sequencing (scRNA-seq) was performed on one CTB and one pHC neonate, with comparative data from one ATB patient.

Main Results:

• CTB neonates showed lymphocyte depletion, reduced regulatory T (Treg) cells, and an excessive innate immune response.
• scRNA-seq revealed suppressed immune function in T and natural killer (NK) cells in CTB neonates.
• Myeloid cells in CTB neonates exhibited an activated inflammatory response, with transcriptomic similarities to ATB but weaker antigen presentation capacity.

Conclusions:

• CTB is associated with significant immune dysregulation, including impaired adaptive immunity and heightened innate inflammation.
• These immune alterations may partially explain the high mortality rate of congenital tuberculosis.
• Further research with larger scRNA-seq cohorts is needed to validate findings and understand CTB pathogenesis.