Immunomodulation and Protective Effects of Cordyceps militaris Extract Against Candida albicans Infection in Galleria mellonella Larvae

<i>Cordyceps militaris</i>-derived formulations are currently used for multiple purposes because of their medical properties, especially immune system modulation. This study analyzes the inhibitory effects of <i>C. militaris</i> aqueous extract on <i>Candida albicans</i> infections and the immune response in larvae of the greater wax moth <i>Galleria mellonella</i> (Lepidoptera: Pyralidae). Larvae exhibited melanization within 1 h of being infected with <i>C. albicans</i> inoculum at a concentration of 10⁶ cells/larvae, and died within 24 h from a lethal dose. Aqueous extract of <i>C. militaris</i> proved to be nontoxic at concentrations of 0.25 and 0.125 mg/larvae, and had the greatest ability to prolong the survival of larvae infected with a sublethal dose of <i>C. albicans</i> at a concentration of 10⁵ cells/larvae. Moreover, the number of hemocytes in the hemolymph of <i>G. mellonella</i> increased after infection with <i>C. albicans</i> and treatment with the aqueous extract of <i>C. militaris</i> at 1, 24, and 48 h by 1.21 × 10⁷, 1.23 × 10⁷, and 1.4 × 10⁷ cells/100 µL, respectively. The highest number of hemocytes was recorded after treatment of infected <i>G. mellonella</i> with the extract for 48 h. Transcriptional upregulation of the immune system was observed in certain antimicrobial peptides (AMPs), showing that the relative expression of <i>galiomicin</i>, <i>gallerimycin</i>, and <i>lysozyme</i> genes were upregulated as early as 1 h after infection. Therefore, we conclude that <i>C. militaris</i> aqueous extract can modulate the immune system of <i>G. mellonella</i> and protect against infection from <i>C. albicans</i>.