Streptococcus pneumoniae is a major cause of morbidity and mortality worldwide, and commonly colonizes the upper respiratory tract. In some colonized individuals the organism translocates to other tissues and causes life-threatening diseases including pneumonia, bacteremia, and meningitis. Rates of disease are especially high in the very young and old and in patients with predisposing conditions including HIV infection, cardiopulmonary or co-morbidities, renal diseases including nephrotic syndrome, and sickle cell disease and other causes of hyposplenia.
Approximately 5 million children under the age of 5 years die with a respiratory tract infection every year; the major causative pathogen in these cases is S. pneumoniae (Williams et al. 2002). Pneumococcal infection caused approximately 45,000 deaths in adults in the United States in 1998, about two years prior to the introduction of the 7-valent pneumococcal conjugate vaccine for infants (Robinson et al. 2001). Streptococcus pneumoniae also causes less serious but extremely common diseases such as otitis media, sinusitis and exacerbations of chronic obstructive pulmonary disease. It has been estimated that there are 7 million cases of otitis media in the United States every year (Stool & Field 1989).
OVERVIEW OF PATHOGENESIS
The first step in the pathogenesis of pneumococcal disease is nasopharyngeal colonization, with individuals often carrying more than one serotype at a time. Asymptomatic nasopharyngeal carriage is established when surface components of the pneumococcus bind to nasal epithelium (Tuomanen & Masure 1997; Weiser et al., 1996).
The innate immune system is a set of cellular and humoral components which recognise the general features of microbes in order to clear these potentially damaging agents from the body. In contrast to the acquired immune system this does not require prior exposure to the infectious agent. The development of the innate immune system as a range of pattern recognition receptors (PRRs) designed to recognise pathogen-associated molecular patterns (PAMPs) is a response to the host's inability to store unique recognition molecules for every possible pathogen within the genome.
Mannose-binding lectin (MBL) is a part of the humoral innate immune system. It is a pattern-recognition molecule able to detect a wide range of microbial and altered self-targets and recruit a number of host immune effector systems to clear those targets (Turner, 1996). However, genetic deficiency of MBL is surprisingly common in most human populations (Turner and Hamvas, 2000).
The protein was first discovered through biochemical purification and the gene independently described after functional cloning by two research teams. The effects of human MBL deficiency were documented separately by these research efforts and led in due course to the discovery of the genetic polymorphisms that give rise to this deficiency. More recently, the details of disease susceptibilities and the mechanisms of these effects have been elucidated.
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