Molecular Pathogens, 2025, Vol.16, No.1, 1-9 http://microbescipublisher.com/index.php/mp 5 5.2 Role of toll-like receptors (TLRs) in pathogen recognition TLRs are a special class of receptors that can recognize pathogens such as viruses, bacteria and other pathogens and are the “radars” of the immune system. In buffalo, TLRs can detect various pathogens, such as avian influenza viruses. These receptors also work with other immune signaling pathways (like RIG-I-like receptors). The genes of these receptors show a lot of changes in water buffalo, which means they may have adapted to invasions of different viruses or bacteria (Jax et al., 2022). Although there are not many studies on buffalo TLRs at present, we already know that they play a big role in initiating immune responses (Panigrahia et al., 2016). 5.3 Transcriptomic and proteomic analysis of infected tissues By analyzing gene expression (transcriptionome) and protein changes (proteome) in the tissues after buffalo infection, we can have a clearer understanding of what is happening in their bodies. For example, when water buffalo were infected with giant hepatic flukes, transcriptome studies found that the expression of many cytokines and transcription factors would change at different time points. These changes are related to liver lesion processes and regulation of immune responses. The proteome study also found that some of the proteins released by the parasite interact with the substances in the buffalo’s blood. These proteins may help parasites escape the immune system or interfere with the buffalo’s defense mechanisms (Huang et al., 2019). These studies illustrate the complexity of the buffalo immune response, and also allow us to see new therapeutic directions, such as finding some proteins as drug targets to help water buffalo better fight infections. 6 Environmental and Management Factors Influencing Disease Susceptibility 6.1 Effects of nutrition and stress on immune competence The immunity of water buffalo has a lot to do with whether they eat well and whether they are often stimulated. If water buffalo cannot keep up with their nutrition, their bodies will be prone to problems and their chances of getting sick are higher. Eating well can sometimes make the immune system stronger, and may also make pathogens “eat well” and live longer (Pike et al., 2019). Various stresses can also affect the immune response. Some are caused by nature, such as temperature changes; some are artificial, such as crowding, transportation, water shortage, etc. For example, if water buffalo do not eat enough, they will not be able to reproduce well and the bacteria will not survive long; but environmental pressures like high temperatures will weaken the water buffalo, which will make the bacteria more likely to spread (Vicente-Santos et al., 2023). In some African buffalo studies, it was found that if the nutrition is insufficient and infected with a variety of parasites, the health of the buffalo will be worse. Especially parasites like Schistosoma, they are particularly easy to take advantage of the situation. This also shows that nutrition and immunity are indeed closely related. 6.2 Influence of climate and habitat on disease dynamics The environment in which buffalo lives and the changes in weather will also affect whether they are prone to illness. Environments such as temperature, humidity, and whether living places are clean, will affect the microorganisms in the water buffalo's body, which are important to the immune system (Bernardo-Cravo et al., 2020). Some studies have found that water buffalo are more likely to be infected with parasites when seasons change, such as from dry season to rainy season. Some terrain, such as by ponds or near wetlands, are “hot spots” where pathogens are particularly prone to spread (Beechler et al., 2017). The microorganisms in animals' bodies will also change due to changes in the environment, which will affect immunity and infection. Just like amphibians, once the temperature changes, infections can become more complex and the immune system may become weaker (Herczeg et al., 2021). 6.3 Impact of veterinary interventions and vaccination programs Vaccinating water buffalo or treating them in time can indeed reduce many diseases. For example, studies have found that treatment with praziquantel can significantly reduce the number of eggs and insects caused by schistosomiasis in Japan. This treatment can also help water buffalo become more resistant the next time they encounter infection (He et al., 2018). However, the problem is not that simple. If the buffalo is infected with other bacteria at the same time, their response to the new vaccine may not be very good, and their immunity will be
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