M ycoplasma pneumoniae carriage evades induction of protective mucosal antibodies

Abstract

Background: Mycoplasma pneumoniae is the most common bacterial cause of pneumonia in children hospitalised for community-acquired pneumonia (CAP). Prevention of infection by vaccines may be an important strategy in the presence of emerging macrolide-resistant M. pneumoniae. However, knowledge of immune responses to M. pneumoniae is limited, complicating vaccine design.

Methods: We studied the antibody response during M. pneumoniae respiratory tract infection and asymptomatic carriage in two different cohorts.

Results: In a nested case-control study (n=80) of M. pneumoniae carriers and matched controls we observed that carriage by M. pneumoniae does not lead to a rise in either mucosal or systemic M. pneumoniae-specific antibodies, even after months of persistent carriage. We replicated this finding in a second cohort (n=69) and also found that during M. pneumoniae CAP, mucosal levels of M. pneumoniae-specific IgA and IgG did increase significantly. In vitro adhesion assays revealed that high levels of M. pneumoniae-specific antibodies in nasal secretions of paediatric patients prevented the adhesion of M. pneumoniae to respiratory epithelial cells.

Conclusions: Our study demonstrates that M. pneumoniae-specific mucosal antibodies protect against bacterial adhesion to respiratory epithelial cells, and are induced only during M. pneumoniae infection and not during asymptomatic carriage. This is strikingly different from carriage with bacteria such as Streptococcus pneumoniae where mucosal antibodies are induced by bacterial carriage.

FIGURE 1

Mycoplasma pneumoniae upper respiratory tract colonisation does not induce a mucosal M. pneumoniae-specific antibody response. a–c) Cohort 1 nasal lavage samples of age- and season-matched M. pneumoniae carriers (n=39/40) and healthy controls (n=40/40) were analysed by ELISA for levels of M. pneumoniae-specific a) IgA, b) IgG and c) IgM. d, e) M. pneumoniae-specific d) IgA and e) IgG levels in nasal lavage of M. pneumoniae carriers (n=10) over the course of 2 months. Lines and error bars represent geometric means with 95% confidence interval. ns: nonsignificant (paired t-test).

FIGURE 2

Mycoplasma pneumoniae infection induces an increase in mucosal M. pneumoniae-specific antibody levels. a, b) Cohort 2 nasal lavage samples of M. pneumoniae community-acquired pneumonia (CAP) (n=9–15/18) and non-M. pneumoniae CAP patients (n=14–18/22) were analysed by ELISA for levels of M. pneumoniae-specific a) IgA and b) IgG. Lines and error bars represent geometric means with 95% CI. c) Genomic copy numbers of M. pneumoniae in the upper respiratory tract as determined by PCR in relation to upper respiratory tract levels of M. pneumoniae-specific IgA in M. pneumoniae CAP patients at >10 days post-onset of symptoms (n=15/18). *: p<0.05; ***: p<0.001; ns: nonsignificant (paired t-test for ≤10 versus >10 days and unpaired t-test for other comparisons).

FIGURE 3

Mycoplasma pneumoniae-specific antibodies in nasal secretions block the adhesion of M. pneumoniae to respiratory epithelial cells. Adhesion of M. pneumoniae to A549 cells in vitro when cultured in the presence or absence of M. pneumoniae-specific antibodies containing nasal lavage from both cohort 1 and 2 (n=33). Number of adhering bacteria (expressed as CFU) in relation to M. pneumoniae-specific a) IgA or b) IgG levels in nasal secretions.