Abstract
Although the effectiveness of BCG vaccination in preventing adult pulmonary tuberculosis (TB) has been highly variable, epidemiologic studies have suggested that BCG provides other general health benefits to vaccinees including reducing the impact of asthma, leprosy, and possibly malaria. To further evaluate whether BCG immunization protects against malarial parasitemia and to define molecular correlates of this non-specific immunity, mice were vaccinated with BCG and then challenged 2 months later with asexual blood stage Plasmodium yoelii 17XNL (PyNL) parasites. Following challenge with PyNL, significant decreases in parasitemia were observed in BCG vaccinated mice relative to naïve controls. To identify immune molecules that may be associated with the BCG-induced protection, gene expression was evaluated by RT-PCR in i) naïve controls, ii) BCG-vaccinated mice, iii) PyNL infected mice and iv) BCG vaccinated/PyNL infected mice at 0, 1, 5, and 9 days after the P. yoelii infection. The expression results showed that i) BCG immunization induces the expression of at least 18 genes including the anti-microbial molecules lactoferrin, eosinophil peroxidase, eosinophil major basic protein and the cathelicidin-related antimicrobial peptide (CRAMP); ii) an active PyNL infection suppresses the expression of important immune response molecules; and iii) the extent of PyNL-induced suppression of specific genes is reduced in BCG-vaccinated/PyNL infected mice. To validate the gene expression data, we demonstrated that pre-treatment of malaria parasites with lactoferrin or the cathelicidin LL-37 peptide decreases the level of PyNL parasitemias in mice. Overall, our study suggests that BCG vaccination induces the expression of non-specific immune molecules including antimicrobial peptides which may provide an overall benefit to vaccinees by limiting infections of unrelated pathogens such as Plasmodium parasites.
Highlights
Mycobacterium bovis BCG has been used globally as a vaccine against tuberculosis (TB) for more than eight decades
To characterize the impact that BCG immunization has on the course of malaria infections, we evaluated whether BCG vaccination protected against PyNL infections of mice
After an erythrocytic infection with the PyNL strain, the peak of parasitemia is generally observed at 12–14 days post-infection and the parasites are generally cleared at about 3–4 weeks after the infection
Summary
Mycobacterium bovis BCG has been used globally as a vaccine against tuberculosis (TB) for more than eight decades. The effectiveness of BCG vaccination in preventing pulmonary TB is uncertain because efficacy estimates from controlled clinical trials have varied between 0–80%, BCG has consistently been shown to protect against severe disseminated forms of TB in infants [1,2]. Several studies have supported these initial findings by showing that BCG vaccination imparts wide ranging beneficial health-related effects that are not directly related to its anti-tuberculosis activity. Epidemiologic data has shown that BCG vaccination was associated with a 45% decrease in infant mortality in Guinea-Bissau and Benin [4,5]. This non-specific effect of BCG immunization transcended its impact on reducing disseminated childhood TB. Intravesical BCG therapy has been the treatment of choice for several forms of bladder cancer because of the potent anti-tumor activity of BCG [8]
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