Protective effect of a novel antifungal peptide derived from human chromogranin a on the immunity of mice infected with Candida krusei

Abstract

Invasive fungal infections threat the life of immunocompromised patients. Chromogranin A N-46 (CGA-N46), corresponding to the 31st to 76th amino acids of the N-terminus of human chromogranin A, is an antifungal peptide. In order to elucidate the antifungal effects of CGA-N46 in vivo, we studied its effects on cell-mediated immunity in Candida krusei-infected mice. The results showed that the treatment with CGA-N46 increased the average body weight and decreased the mortality of the immunocompromised mice model infected with Candida krusei. The spleen and thymus indices of treated mice has markedly increased compared with that of the control group (P<0.05), and the immune cell levels in peripheral blood also increased significantly (P<0.05). The immuno-modulatory effect of CGA-N46 (60 mg/kg/day) was found to be comparable to that of terbinafine. Additionally, CGA-N46 could alleviate or eliminate histopathological symptoms in the liver, spleen, kidney, and lung tissues. In conclusion, the present study suggests that CGA-N46 may offer a new strategy for antifungal therapeutic option. This study is an essential step in elucidating the effect of CGA-N46 in vivo.

Keywords: CGA-N46; antifungal peptide; chromogranin A; immuno-modulatory effect; immunocompromised Candida krusei-infected mice model; protective effect.

Figure 1.

The average body weights of (A) the survival mice and (B) the survival rates of each tested group. Data were represented as mean ± SEM. Differences between groups were considered to be statistically significant at P<0.05 and shown as different letters. The different letter above the bar means significant difference between groups. The same letter above the bar means no significant differences.

Figure 2.

The effect of CGA-N46 on (A) thymus index and (B) spleens index. Differences between groups were considered to be statistically significant at P<0.05 and shown as different letters. The different letter above the bar means significant difference between groups. The same letter above the bar means no significant differences.

Figure 3.

The effect of CGA-N46 on (A) white blood cells, (B) lymphocytes, (C) monocytes, and (D) neutrophil granulocytes. Differences between groups were considered to be statistically significant at P<0.05 and shown as different letters. The different letter above the bar means significant difference between groups. The same letter above the bar means no significant differences.

Figure 4.

Histopathological changes of tissues on day 14 of CGA-N46 treatment. H&E staining. A, alveolar interstitial lymphocytes infiltration; B, hepatic cord; C, nuclear pyknosis; D, nuclear dissolution; E, white pulp; F, red pulp; G, the boundaries between the red pulp and white pulp; H, structural disordered splenic corpuscles; I, macrophages; J, bleeding; K, swelling of the glomerulus; L, inflammatory cells.