Importantly, the induction of STAT6-dependent pathways by Pneumocystis recently documented in rodents can result in clinico-pathological consequences, including Pneumocystis-induced airway hyperresponsiveness (AHR) [12], therefore underscoring the need for further study of these mechanisms in human lungs. Mucus-associated up-regulation by Pneumocystis may be theoretically

relevant in different scenarios. For example, as a co-factor in increasing severity of respiratory illnesses during infancy, when narrow developing airways are present. Pneumocystis colonization is highly prevalent in infants, affecting over 90% of infants between 2 and 5 months of age, when respiratory morbidity typically increases [2]. Results may also strengthen the association between SNS-032 in vitro Pneumocystis and severity of

COPD [3]; a disease that is strongly associated Adriamycin purchase with increased mucus compromising narrow airways in immunocompetent adults [4], [21] and [22]. Overexpression of mClca3 induces mucous cell metaplasia, airway hyperreactivity (AHR) and increased airway resistance in immunocompetent rodents, and is also correlated with increased MUC5AC levels [6] and [7]. Recent studies using microarray technology on lung samples from patients diagnosed with COPD found Pneumocystis-related overexpression of proteins that are predominantly Acyl CoA dehydrogenase expressed on activated Th 1 T-lymphocytes showing the complexity of this Pneumocystis host interaction [23]. A more complete characterization of the immune response to Pneumocystis in these infants might lead to understand any potential role

in disease. It is well known that respiratory viruses are associated with mucus hypersecretion, including increased expression of MUC5AC [4], [6] and [7]. Therefore, we were expecting to detect an additive increase of hCLCA1 in samples where Pneumocystis and viruses were associated. Unfortunately, the limited number of virus-positive specimens detected using DNA/RNA amplification techniques in this study precluded us from identifying any relationship between common respiratory viruses and increased hCLCA1 or MUC5AC. The 20% pooled detection rate for viruses is similar to previous studies published by our group on autopsied infant lungs using viral cultures and immunofluorescence [24]. Pneumocystis is highly endemic in infants, while viruses follow epidemic patterns. Viruses are of low prevalence in these type of infant samples [25]. The viruses that were examined in these samples were the same as previously identified using other techniques [24].