Fungal colonization with Pneumocystis correlates to increasing chloride channel accessory 1 (hCLCA1) suggesting a pathway for up-regulation of airway mucus responses, in infant lungs.
Fungal colonization with Pneumocystis is associated with increased airway mucus in infants during their primary Pneumocystis infection, and to severity of COPD in adults. The pathogenic mechanisms are under investigation. Interestingly, increased levels of hCLCA1 - a member of the calcium-sensitive chloride conductance family of proteins that drives mucus hypersecretion - have been associated with increased mucus production in patients diagnosed with COPD and in immunocompetent rodents with Pneumocystis infection. Pneumocystis is highly prevalent in infants; therefore, the contribution of Pneumocystis to hCLCA1 expression was examined in autopsied infant lungs. Respiratory viruses that may potentially increase mucus, were also examined. hCLCA1 expression was measured using actin-normalized Western-blot, and the burden of Pneumocystis organisms was quantified by qPCR in 55 autopsied lungs from apparently healthy infants who died in the community. Respiratory viruses were diagnosed using RT-PCR for RSV, metapneumovirus, influenza, and parainfluenza viruses; and by PCR for adenovirus. hCLCA1 levels in virus positive samples were comparable to those in virus-negative samples. An association between Pneumocystis and increased hCLCA1 expression was documented (P=0.028). Additionally, increasing Pneumocystis burden correlated with increasing hCLCA1 protein expression levels (P=0.017). Results strengthen the evidence of Pneumocystis-associated up-regulation of mucus-related airway responses in infant lungs. Further characterization of this immunocompetent host-Pneumocystis-interaction, including assessment of potential clinical significance, is warranted.
Programa de Microbiología y Micología, Instituto de Ciencias Biomédicas, Facultad de Medicina Universidad de Chile, Santiago 8380453, Chile.
Francisco J
FJ
Pérez
Programa de Microbiología y Micología, Instituto de Ciencias Biomédicas, Facultad de Medicina Universidad de Chile, Santiago 8380453, Chile.
Carolina A
CA
Ponce
Programa de Microbiología y Micología, Instituto de Ciencias Biomédicas, Facultad de Medicina Universidad de Chile, Santiago 8380453, Chile.
Diego A
DA
Rojas
Programa de Microbiología y Micología, Instituto de Ciencias Biomédicas, Facultad de Medicina Universidad de Chile, Santiago 8380453, Chile.
Pablo A
PA
Iturra
Programa de Microbiología y Micología, Instituto de Ciencias Biomédicas, Facultad de Medicina Universidad de Chile, Santiago 8380453, Chile.
Rebeca I
RI
Bustamante
Servicio Médico Legal, Santiago 8380454, Chile.
Myriam
M
Gallo
Servicio Médico Legal, Santiago 8380454, Chile.
Karime
K
Hananias
Programa de Microbiología y Micología, Instituto de Ciencias Biomédicas, Facultad de Medicina Universidad de Chile, Santiago 8380453, Chile.
Sergio L
SL
Vargas
Airway; Immunocompetent; Pneumocystis jirovecii; Primary infection