Pretreatment with Antibiotics Impairs Th17-Mediated Antifungal Immunity in Newborn Rats
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ORIGINAL ARTICLE
Pretreatment with Antibiotics Impairs Th17-Mediated Antifungal Immunity in Newborn Rats Ping Wang ,1,2 Jie Yao,1 Li Deng,1 Xiaoqi Yang,1 Wei Luo,1 and Wei Zhou1,2
Abstract— Clinical studies have confirmed that the use of antibiotics, especially carbapenems, is a high-risk factor for fungal infection in preterm infants. However, it is not entirely clear whether the increased risk for fungal infection is due to the immune differences in preterm infants or antibiotic usage. We found that after newborn rats received antibiotics, they exhibited significantly impaired anti–Candida albicans immunity in comparison with those without treatment, as shown by significantly increased levels of fungal glucan in the peripheral blood, multiple caseous fungal infections in the abdominal cavity, intestinal congestion, ischemia, and a decrease in the number of intestinal villi. Mechanistically, pretreatment with antibiotics diminished antifungal innate immunity by TLR2 and inhibited IL-17A release and neutrophil recruitment, leading to increased susceptibility to fungi. In summary, we demonstrate that antibiotic usage impairs antifungal immunity in neonates and suggest that antifungal prophylaxis may be required after antibiotic treatment in high-risk preterm babies. KEY WORDS: antifungal immune regulation; antibiotics; IL-17; TLRs; gut microbiota.
BACKGROUND Fungal infection in preterm infants is a serious disease in the neonatal intensive care unit, and it will prolong hospitalization time and affect the prognosis of preterm infants. Antibiotics are recognized and their use is supported by evidence such as the highrisk factors for fungal infection in preterm infants [1, 2]. Different helper T cell (Th) subsets play different roles in fungal immunity, with Th1 and Th17 1
Department of Neonatology, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, China 2 To whom correspondence should be addressed at Department of Neonatology, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, China. E-mails: [email protected]; [email protected]
protecting against fungi. After activation, Th17 cells produce cytokines such as interleukin (IL)-17A, chemotactic phagocytes, and neutrophils [3–5]; induce inflammation and anti-microbial reaction [6]; and play an important role in antifungal immune protection [7–12]. Research is constantly revealing the close relationship between intestinal microecology and cellular immunity, and an increasing number of studies based on intestinal microecology suggest that the change in intestinal flora caused by the use of antibiotics and other reasons will result in abnormal immune function, reduce the immune defense function of the body against a variety of pathogens, and increase susceptibility to pathogens [13]. However, how antibiotics affect the antifungal immune function and promote the susceptibility of premature infants to fungi remains unclear.
0360-3997/20/0000-0001/0 # 2020 Springer Science+Business Media, LL
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