Levels of the serum opsonin mannan-binding lectin (MBL) were directly correlated with the probability of developing visceral leishmaniasis. Monocytes infected with MBL-opsonized Leishmania chagasi promastigotes secreted higher levels of tumor necrosis factor alpha and interleukin-6 than cells infected with nonopsonized parasites. Our findings indicate that MBL can modulate the clinical outcome of infection with L. chagasi and the function of infected macrophages.Visceral leishmaniasis (VL) in Brazil is caused by the intracellular pathogen Leishmania chagasi and is almost always lethal if not treated (4). A persisting question has been why only a small proportion of infected individuals develop disease (4). Most infections will remain cryptic unless immunological suppression occurs (2). Young age, malnutrition, and human immunodeficiency virus infection are risk factors for VL (2, 4), but other host susceptibility factors remain unknown. Mannanbinding lectin (MBL), a multichain serum lectin and a component of innate immunity (10), is a candidate molecule for modifying disease progression because of its possible enhancing effect upon infections with intracellular pathogens (13,14). It binds to carbohydrates present on many pathogens, including Leishmania (14), acting as an opsonin and "ante-antibody" by conferring protection before the establishment of adaptive immune responses (11). Three independent mutations at exon 1 result in amino acid substitutions in a collagenous region of the polypeptide chain (20, 28), which hinder assembly of subunits into the functional trimeric structure, render them vulnerable to degradation (18), and affect levels of MBL in serum.Garred and colleagues proposed a dual role for MBL that explains the selective advantage for the wide range in levels of this collectin seen in a population (13): whereas low concentrations or exon 1 mutations have been associated with recurrent or severe infections in children and adults caused by extracellular pathogens (16,29) and Plasmodium falciparum (19), high concentrations may enhance targeting of intracellular organisms to host phagocytes, the milieu preferred by these pathogens. We addressed this hypothesis by evaluating levels of MBL in VL in a case-control study of a population from Teresina, Piauí State, Brazil, where urban epidemics have occurred since 1980 (8) and where there is no transmission of Chagas' disease or cutaneous leishmaniasis. Individuals presenting with active VL (aVL) or a documented history of this disease and cured for at least 5 months (median, 316 days) (cVL) before sample collection were compared with healthy, Montenegro (leishmanin) skin test (MST)-positive or MSTnegative individuals recruited from the same background and with no history of VL. Informed consent and institutional approval were obtained. Individuals were between 1 and 80 years of age (mean, 22.5 Ϯ 16.2 years) and represent an admixture of African, Caucasian, and native American populations estimated, respectively, at 31, 21, and 48% (3). Diagnosis of VL w...
