Beneficial effects of a low-protein diet on host resistance to Paracoccidioides brasiliensis in mice.
OBJECTIVE
Although protein malnutrition impairs immune functions, several studies have recently shown that protein restriction without malnutrition is beneficial to host defenses against invading pathogens and cancer. In an effort to establish the optimum diet for host resistance, we investigated the effect of different dietary protein levels on host resistance to Paracoccidioides brasiliensis.


METHODS
Mice were fasted for 2 days and then infected with P. brasiliensis. Immediately after challenge with this fungus, mice were refed on diets with three different levels (0%, 1.5%, or 20%) of casein. On days 0-7 after infection, antifungal activity and levels of proinflammatory mediators in the spleen and liver were measured.


RESULTS
Mice refed on the 1.5% casein diet showed higher antifungal activity in the spleen and liver compared with mice on the 20% casein diet. The antifungal activity in the spleens of mice refed on the 0% casein diet was intermediate between the antifungal activities of those refed the 1.5% and 20% casein diets. After infection, increases in spleen and liver levels of interleukin-6 and interferon-gamma, liver mRNA levels of antimicrobial proteins (myeloperoxidase, cathepsin-G, and elastase-2), and liver mRNA levels of proinflammatory mediators (interleukin-18, chemokine C-X-C motif ligand 10, nuclear factor-kappaB, inducible nitric oxide synthase, and granulocyte-macrophage colony-stimulating factor) were less profound in mice on the 1.5% or 0% casein diet compared with mice refed the 20% casein diet.


CONCLUSIONS
The present results suggest that protein restriction without malnutrition could be beneficial to host resistance to P. brasiliensis.
Oarada
Motoko
M
Medical Mycology Research Center, Chiba University, Chiba, Japan. motoko.o@faculty.chiba-u.jp
Kamei
Katsuhiko
K
Gonoi
Tohru
T
Tsuzuki
Tsuyoshi
T
Toyotome
Takahito
T
Hirasaka
Katsuya
K
Nikawa
Takeshi
T
Sato
Ayaka
A
Kurita
Nobuyuki
N
D000818:Animals; D002364:Caseins / Q000494:pharmacology*; D056649:Cathepsin G; D002403:Cathepsins / Q000378:metabolism; D018753:Diet, Protein-Restricted; D004305:Dose-Response Relationship, Drug; D005260:Female; D015870:Gene Expression; D007113:Immunity, Innate; D007371:Interferon-gamma / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D010228:Paracoccidioides; D010229:Paracoccidioidomycosis / Q000178:diet therapy* / Q000276:immunology; D009195:Peroxidase / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D012697:Serine Endopeptidases / Q000378:metabolism; D013154:Spleen / Q000187:drug effects / Q000276:immunology / Q000378:metabolism
D002364:Caseins; D015850:Interleukin-6; D012333:RNA, Messenger; D007371:Interferon-gamma; D009195:Peroxidase; D002403:Cathepsins; D012697:Serine Endopeptidases; D056649:Cathepsin G; C534096:Ctsg protein, mouse; C117309:pancreatic elastase II