Phagocytosis and Killing of Common Bacterial Pathogens of the Lung by Human Alveolar Macrophages

Abstract

To investigate factors that determine susceptibility of the lungs to infection with common respiratory pathogens, we studied phagocytosis and killing of nontypable Haemophilus influenzae, H. influenzae type b, Streptococcus pneumoniae types III, VI, and XIV, an unencapsulated variant of S. pneumoniae type III, and Staphylococcus aureus Cowan I, by using human alveolar macrophages obtained by bronchoalveolar lavage of healthy nonsmokers. After opsonization with 10% pooled human serum, mean uptake (+/- standard deviation) of nontypable H. influenzae (67.5% +/- 15.0%), unencapsulated S. pneumoniae type III (71.2% +/- 4.8%) and S. aureus (79.1% +/- 10.2%) was significantly greater (P less than .01) than that of H. influenzae type b (40.1% +/- 15.0%), and S. pneumoniae types III (4.4% +/- 3.1%), VI (11.8% +/- 9.6%), or XIV (8.7% +/- 7.0%). Nontypable H. influenzae was ingested after opsonization with much less pooled human serum than was H. influenzae type b, and uptake of encapsulated S. pneumoniae was not enhanced by as much as 80% pooled human serum. Intracellular killing of unencapsulated S. pneumoniae type III and nontypable H. influenzae was rapid and complete and corresponded to the degree of phagocytosis, but despite a high uptake, S. aureus were killed slowly and incompletely. The virulence of S. pneumoniae and H. influenzae as lung pathogens is thus determined jointly by encapsulation and the inadequate opsonizing effect of normal human serum, whereas that of S. aureus may be related to the organism's relative resistance to intracellular killing by alveolar macrophages.

Alveolar Macrophage Apoptosis Contributes to Pneumococcal Clearance in a Resolving Model of Pulmonary Infection

“…AM are the resident phagocytes of the lung and play a critical role in the innate defense against bacteria (7,8,11). Previous studies have investigated the effect of AM depletion, using liposome-encapsulated clodronate, on the host response to pulmonary infections (34, 44 -47).…”

“…Nevertheless, the development of pneumonia is relatively rare (1,5), which reflects the efficiency of host factors in preventing the development of pneumococcal pneumonia (6). Alveolar macrophages (AM) 3 contribute to the early stages of innate defense against bacteria in the lung by phagocytosing bacteria that reach the terminal bronchioles and alveoli (7,8). Macrophages generate antimicrobial molecules, secrete cytokines, and present Ags, hence linking innate to adaptive immunity (9).…”

Current Understanding of Streptococcal Urinary Tract Infection

“…Several virulence factors of GBS including LTA, -hemolysin, C5a peptidase and the R protein/antigen are involved in recognition by host cells and inducing or evading immune www.intechopen.com responses (Cheng et al, 2001, Fasola et al, 1996, Henneke et al, 2005. The proficiency of GBS recognition by macrophages is considered a crucial component of early immune responses against the bacteria (Chattopadhyay et al, 2011, Franke-Ullmann et al, 1996, Jonsson et al, 1985, Sherman et al, 1992, Sibille&Reynolds, 1990). However, GBS are able to persist inside macrophages for an extended period of time after nonopsonic phagocytosis and eventually trigger death of the host cell (Cornacchione et al, 1998, Fettucciari et al, 2000, Ulett et al, 2003, Valenti-Weigand et al, 1996.…”

Respiratory infections: Proceedings of the Eighth Liverpool Tropical School Bayer Symposium of Microbial Disease held on 3 February 2001

“…In particular, rat alveolar macrophages do not ingest or kill pneumococci effectively, but rabbit alveolar macrophages ingest and kill the bacteria very rapidly, whereas guinea-pig macrophages are intermediate between the two. Work on human alveolar macrophages has consistently shown very low rates of pneumococcal ingestion except when non-capsulate organisms were studied [39]. Secondly, there is considerable heterogeneity in the human alveolar macrophage population in any individual sample [40].…”