Abstract
Anopheles mosquito midgut harbors a diverse group of endogenous bacteria that grow extensively after the blood feeding and help in food digestion and nutrition in many ways. Although, the growth of endogenous bacteria is regulated by various factors, however, the robust antibacterial immune reactions are generally suppressed in this body compartment by a heme peroxidase HPX15 crosslinked mucins barrier. This barrier is formed on the luminal side of the midgut and blocks the direct interactions and recognition of bacteria or their elicitors by the immune reactive midgut epithelium. We hypothesized that in the absence of HPX15, an increased load of exogenous bacteria will enormously induce the mosquito midgut immunity and this situation in turn, can easily regulate mosquito-pathogen interactions. In this study, we found that the blood feeding induced AsHPX15 gene in Anopheles stephensi midgut and promoted the growth of endogenous as well as exogenous fed bacteria. In addition, the mosquito midgut also efficiently regulated the number of these bacteria through the induction of classical Toll and Imd immune pathways. In case of AsHPX15 silenced midguts, the growth of midgut bacteria was largely reduced through the induction of nitric oxide synthase (NOS) gene, a downstream effector molecule of the JAK/STAT pathway. Interestingly, no significant induction of the classical immune pathways was observed in these midguts. Importantly, the NOS is a well known negative regulator of Plasmodium development, thus, we proposed that the induction of diverged immune pathways in the absence of HPX15 mediated midgut barrier might be one of the strategies to manipulate the vectorial capacity of Anopheles mosquito.
Highlights
The tropical region of the world pays a heavy toll to malaria in terms of death and economic loss
It is an excellent system to understand the interaction of innate immunity, exogenous food and endogenous natural microbial habitats
It is noteworthy to mention that a fine balance between the innate immunity and digestion process is required to drive the physiological functions of the midgut over the immune reactivity against bolus antigens
Summary
The tropical region of the world pays a heavy toll to malaria in terms of death and economic loss. World Health Organization reported 214 million cases and 438,000 deaths from malaria in 2015 (WHO, 2015). This situation certainly warrants attention to develop effective methods for malaria prevention. A number of strategies such as, discovery of effective vaccine/drug against malaria. Anopheles HPX15 Modulates Midgut Immunity parasite Plasmodium and numerous vector control measures are worth mentioning here. Arresting Plasmodium development inside the mosquito host and developing transmission blocking strategies may be promising in controlling malaria spread among the human hosts. Plasmodium undergoes a series of complex developmental transitions and majority of parasites are killed during this process (Ghosh et al, 2000; Sinden and Billingsley, 2001; Pradel, 2007). It is of note that the number of Plasmodium is regulated by the ingested blood factors as well as mosquito innate immunity (Lensen et al, 1998; Michel and Kafatos, 2005; Vlachou et al, 2005; Ramiro et al, 2011; Simon et al, 2013)
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