Immune characteristics of Plasmodium reinfections in mice following chloroquine cure of primary Plasmodium infections

Abstract

To investigate the disease progression and immunoprotective characteristics in mice re-infected with homogeneous/heterogeneous Plasmodium strains following cure of Plasmodium infections with chloroquine at the peak of parasitemia. C57BL/6 mice were infected with the non-lethal P. yoelii 17XNL strain, and half of mice were given treatment with chloroquine at the peak of parasitemia (9 days post-infection), while the other mice were self-cured naturally. Then, all cured mice were re-infected with the equivalent lethal P. yoelii 17XL or P. berghei ANKA strain 90 days following primary Plasmodium infections. The parasitemia levels during primary infections and reinfections were measured by microscopic examinations of Giemsa-stained thin blood films, and the levels of the IgG antibody in sera and the percentages of memory T cell subsets in spleen cells were detected in mice using ELISA and flow cytometry before and after parasite reinfections, respectively. Following primary infections with the P. yoelii 17XNL strain, the serum IgG antibody levels were (5.047 ± 0.924) pg/mL in the selfcured mice and (4.429 ± 0.624) pg/mL in the chloroquine-treated mice, respectively (t = 0.437, P > 0.05), which were both significantly higher than that in the uninfected mice (1.624 pg/mL ± 0.280 pg/mL) (F = 22.522, P < 0.01). There was no significant difference in the serum IgG antibody level among self-cured and chloroquine-treated mice re-infected with the P. yoelii 17XL strain or the P. berghei ANKA strain (F = 0.542, P > 0.05); however, the serum IgG antibody levels were all significantly higher in selfcured and chloroquine-treated mice re-infected with the P. yoelii 17XLstrain[(15.487±1.173)pg/mLand(15.965±1.150)pg/mL] or the P. berghei ANKA strain [(14.644 ± 1.523) pg/mL and (15.185 ± 1.333) pg/mL] relative to primary infections (F = 67.383, P < 0.01). There was no significant difference in the proportion of CD4+ [(34.208 ± 2.106), (32.820 ± 1.930), (34.023 ± 2.289), (35.608 ± 1.779) pg/mL] or CD8+ T memory cells [(17.935 ± 2.092), (18.918 ± 2.823), (17.103 ± 1.627), (17.873 ± 1.425) pg/mL] in self-cured and chloroquine-treated mice with primary infections with the P. yoelii 17XNL strain followed by re-infections with the P. yoelii 17XL strain or the P. berghei ANKA strain (F = 0.944 and 0.390, both P > 0.05); however, the proportions of the CD4+ or CD8+ T memory cells were significantly greater in self-cured and chloroquine-treated mice with primary infections with the P. yoelii 17XNL strain followed by re-infections with the P. yoelii 17XL strain or the P. berghei ANKA strain than in mice with primary infections (F = 50.532 and 21.751, both P < 0.01). The cure of murine Plasmodium infections with chloroquine does not affect the production of effective immune protections in mice during parasite re-infections. Following a primary infection, mice show a protection against re-infections with either homogeneous or heterogeneous Plasmodium strains, and a higher-level resistance to re-infections with homogeneous parasite strains is found than with heterogeneous strains.