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Role of pulmonary phagocytes in host defense against group B streptococci in preterm versus term rabbit lung
M P Sherman1, J T Johnson, R Rothlein
1Department of Pediatrics, UCLA School of Medicine 90024-1752.
Abstract:
Intrapulmonary clearance of group B streptococci (GBS) occurred in term rabbits 4 and 8 h after infection; GBS growth was evident in preterm rabbits at 8 h. Bronchoalveolar lavage revealed 17-fold higher numbers of pulmonary alveolar macrophages (PAM) in term versus preterm animals immediately after infection, whereas polymorphonuclear leukocyte (PMNL) recruitment was 13-fold greater in preterm than term rabbits at 8 h. Anti-CD18 monoclonal antibody R15.7 did not reduce PMNL influx or GBS killing in term animals. R15.7 failed to inhibit PMNL influx but augmented GBS growth in preterm animals. R15.7 significantly impaired GBS phagocytosis by preterm and term PMNL in vitro but had no effect on ingestion of GBS by preterm and term PAM. Thus, GBS infection initiates PMNL recruitment into lungs of preterm rabbits by CD18-independent mechanisms, but phagocytosis of GBS by PMNL is largely CD18-dependent. The poorer outcome of GBS pneumonia in preterm versus term newborns may result from low levels of PAM, thereby mandating recruitment of PMNL as a second phagocytic defense.
Insights
Group B streptococci (GBS) clearance differs between preterm and term rabbits. Preterm rabbits show impaired GBS phagocytosis by neutrophils, potentially explaining poorer pneumonia outcomes.
Area of Science:
- Immunology
- Neonatal Research
- Microbiology
Background:
- Group B streptococci (GBS) pose a significant threat to newborns, causing severe pneumonia.
- Immune responses in preterm neonates are less developed than in term neonates, impacting infection outcomes.
- Pulmonary alveolar macrophages (PAM) and polymorphonuclear leukocytes (PMNL) are key immune cells in lung infections.
Purpose of the Study:
- To investigate the role of CD18-mediated mechanisms in intrapulmonary GBS clearance in term versus preterm rabbits.
- To compare the recruitment and phagocytic functions of pulmonary immune cells in response to GBS infection in different gestational ages.
Main Methods:
- GBS infection was induced in term and preterm rabbits.
- Bronchoalveolar lavage was performed to quantify PAM and PMNL.
- The effect of anti-CD18 monoclonal antibody (R15.7) on PMNL influx, GBS killing, and phagocytosis was assessed in vivo and in vitro.
Main Results:
- Term rabbits cleared GBS efficiently, while preterm rabbits showed GBS growth.
- Preterm rabbits had lower PAM but higher PMNL recruitment compared to term rabbits.
- Anti-CD18 antibody impaired PMNL phagocytosis of GBS but did not affect PMNL influx or PAM phagocytosis.
Conclusions:
- GBS pneumonia outcomes in preterm neonates may be linked to insufficient PAM and a reliance on CD18-independent PMNL recruitment.
- CD18-dependent phagocytosis by PMNL is crucial for controlling GBS infection in the lungs.
- Targeting CD18-independent pathways or enhancing PAM function could be therapeutic strategies for neonatal GBS pneumonia.