*7.5.1 Moxifloxacin/HBD2*

*Immune Response Activation and Immunomodulation*

HBD2 has a broad spectrum of activity against a wide variety of bacteria, fungi and viruses. The mechanism of action of this defensin begins with the interaction of the negative charges of the pathogen membrane, the formation of pores and finally the lysis of the microorganism. The variability of the composition of the membranes of the different pathogens explains in part the different antimicrobial

HBD2 is important in innate immunity and constitutes the first line of host defense against infections by microorganisms. Its role in adaptive immunity is attributed mainly to its chemotactic activity in immature dendritic cells and

Several mechanisms have been proposed for HBD2 that contributes to the adaptive immunity: (a) Increase in the recruitment of immature dendritic cells. Immature dendritic cells are recruited from circulating blood or tissue near the site of inflammation by chemoattractants that interact with their corresponding receptors (CCR1, CCR5, CCR6). (b) Formation of defensin-antigen complexes. HBD2 forms defensin-antigen complexes facilitating the presentation to dendritic cells. (c) Maturation of dendritic cells. HBD2 induced the maturation of dendritic cells for direct production of IL-2 or indirect production of TNF and IL-1 by monocytes and macrophages. (d) Recruitment of memory T cells. It facilitates the recruitment

of memory T cells that are the effector cells of adaptive immunity [15, 26].

HBD2 contributes to unite the innate and adaptive immune response, and this property has been applied for the development of vaccine adjuvants, since it promotes adaptive immunity when it is administered together with antigens [15, 26].

Inflammation is a protective reaction by the host to eliminate injurious stimuli

HBD2 plays a critical role in regulating inflammation processes in the respiratory system and modulates the production of inflammatory cytokines and chemokines. An increase in local expression has been observed; but in severe cases, the HBD2

HBD-2 can promote histamine release and prostaglandin D2 production in mast

HBD2 and the complement system are two important innate immune mechanisms against a broad range of microorganisms. The complement is composed of more than 30 proteins found in the human serum, and it is activated by three different pathways (classical, alternative and lectin) [73, 74]. It has been described that HBD2 binds to C1q (first component of the complement system) and inhibits the classical complement pathway. HBD2 have a dual protective role not only as an antimicrobial agent but also to provide protection against uncontrolled activation of

(microorganism, damage cell or irritants). Some viral infections cause severe inflammation, and the tissue can be damaged and then it must be repaired. The mechanisms include the production of anti-inflammatory cytokines, lipid media-

**7.1 Antimicrobial activities**

**7.2 Innate and adaptive immunity**

memory T lymphocytes through the CCR6 receptor [26].

tors, glucocorticoids, immune cell apoptosis, etc. [3].

cells, suggesting a role in allergic reactions [1, 26, 72].

can be detected systemically [71].

**7.4 Anti-inflammatory activity**

complement system [73, 75, 76].

effects [2, 22].

**7.3 Inflammation**

**58**

In a study with epithelial lung cells (A549) stimulated with LPS, it was demonstrated that the association of moxifloxacin/HBD2 has an anti-inflammatory effect. Moxifloxacin is a fluoroquinolone against Gram-positive and Gram-negative bacteria, which may have affected the immune system. The treatment induced a reduction of proinflammatory cytokines (IL-1 and IL-6). These data support the hypothesis of its immunomodulatory capacity of HBD2 to neutralize the components of bacteria that induce the activation of cytokines [78].
